Development of a human three-dimensional organotypic skin-melanoma spheroid model for in vitro drug testing
Open accessAbstract
Despite remarkable efforts, metastatic melanoma (MM) still presents with significant mortality. Recently, mono-chemotherapies are increasingly replenished by more cancer-specific combination therapies involving death ligands and drugs interfering with cell signaling. Still, MM remains a fatal disease because tumors rapidly develop resistance to novel therapies thereby regaining tumorigenic capacity. Although genetically engineered mouse models for MM have been developed, at present no model is available that reliably mimics the human disease and is suitable for studying mechanisms of therapeutic obstacles including cell death resistance. To improve the increasing requests on new therapeutic alternatives, reliable human screening models are demanded that translate the findings from basic cellular research into clinical applications. By developing an organotypic full skin equivalent, harboring melanoma tumor spheroids of defined sizes we have invented a cell-based model that recapitulates both the 3D organization and multicellular complexity of an organ/tumor in vivo but at the same time accommodates systematic experimental intervention. By extending our previous findings on melanoma cell sensitization toward TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) by co-application of sublethal doses of ultraviolet-B radiation (UVB) or cisplatin, we show significant differences in the therapeutical outcome to exist between regular two-dimensional (2D) and complex in vivo-like 3D models. Of note, while both treatment combinations killed the same cancer cell lines in 2D culture, skin equivalent-embedded melanoma spheroids are potently killed by TRAIL+cisplatin treatment but remain almost unaffected by the TRAIL+UVB combination. Consequently, we have established an organotypic human skin-melanoma model that will facilitate efforts to improve therapeutic outcomes for malignant melanoma by providing a platform for the investigation of cytotoxic treatments and tailored therapies in a more physiological setting.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In melanoma spheroids, fibroblasts have been shown to accumulate in low-oxygen regions and upregulate genes associated with ECM production and wound response.
“In melanoma spheroids, for example, fibroblasts have been shown to accumulate in low-oxygen regions and upregulate genes associated with ECM production and wound response [288].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [288]
The Results section describes a low-oxygen center in melanoma spheroids, while the Methods section places fibroblasts in the surrounding collagen scaffold. Neither passage reports fibroblasts accumulating in low-oxygen regions or upregulating ECM-production or wound-response genes. Searches for fibroblast localization, hypoxia, and those gene-expression terms found no supporting passage in our copy. (LLM, conf=0.72)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Improved survival with vemurafenib in melanoma with BRAF V600E mutation
Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., Dummer, R., Garbe, C., Testori, A., Maio, M., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103782 · Cited by 7,720 · see citing works
Final Version of 2009 AJCC Melanoma Staging and Classification
Balch, C. M., Gershenwald, J. E., Soong, S.-J., Thompson, J. F., Atkins, M. B., Byrd, D. R., Buzaid, A. C., Cochran, A. J., Coit, D. G., Ding, S., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.23.4799 · Cited by 4,592 · cited 1× · see citing works
“metastatic melanoma (MM) is particularly poor with stage IV patients having a median survival of B8±2 months.(1) Malignant transformation of melanocytes involves stepwise tumor progression.”
BackgroundInhibition of Mutated, Activated BRAF in Metastatic Melanoma
Flaherty, K. T., Puzanov, I. J., Kim, K. B., Ribas, A., McArthur, G. A., Sosman, J. A., O'Dwyer, P. J., Lee, R. J., Grippo, J. F., Nolop, K. B., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1002011 · Cited by 3,542 · cited 1× · see citing works
“Therefore, alternative therapeutic strategies are required, and the targeting of specific activating mutations in melanoma has been of particular interest, yet almost invariably, responders develop therapy resistance.(11)”
BackgroundGenomic responses in mouse models poorly mimic human inflammatory diseases
Seok, J., Warren, H. S., Cuenca, A. G., Mindrinos, M. N., Baker, H. V., Xu, W., Richards, D. R., McDonald-Smith, G. P., Gao, H., Hennessy, L., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1222878110 · Cited by 3,005 · see citing works
Multicellular tumor spheroids: An underestimated tool is catching up again
Hirschhaeuser, F., Menne, H., Dittfeld, C., West, J., Mueller-Klieser, W., & Kunz-Schughart, L. A. (2010) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2010.01.012 · Cited by 1,674 · cited 2× · see citing works
“nodes, micrometastasis or inter-capillary micro regions of solid tumors (Figure 2a).(16,17) We next inserted a defined number of these spheroids (10)”
BackgroundMethodRecent advances in three‐dimensional multicellular spheroid culture for biomedical research
Lin, R., & Chang, H. (2008) · Biotechnology Journal · doi:10.1002/biot.200700228 · Cited by 1,264 · cited 1× · see citing works
“Only spheroids with sizes of/above 500mm represent typical features of nonvascularized tumor tissue.(16,31) To date, conventional chemotherapy-based cancer treat-”
BackgroundRoesch, A., Fukunaga‐Kalabis, M., Schmidt, E. C., Zabierowski, S. E., Brafford, P. A., Vultur, A., Basu, D., Gimotty, P. A., VOGT, T. M., & Herlyn, M. (2010) · Cell · doi:10.1016/j.cell.2010.04.020 · Cited by 1,162 · see citing works
Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors
Wilson, T. R., Fridlyand, J., Yan, Y., Penuel, E., Burton, L., Chan, E., Peng, J., Lin, E., Wang, Y., Sosman, J., et al. (2012) · Nature · doi:10.1038/nature11249 · Cited by 1,134 · see citing works
Chapman, P. B., Einhorn, L. H., Meyers, M. L., Saxman, S. B., Destro, A. N., Panageas, K. S., Begg, C. B., Agarwala, S. S., Schuchter, L. M., Ernstoff, M. S., et al. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.9.2745 · Cited by 763 · see citing works
ABCB5-Mediated Doxorubicin Transport and Chemoresistance in Human Malignant Melanoma
Frank, N. Y., Margaryan, A., Huang, Y. S., Schatton, T., Waaga-Gasser, A. M., Gasser, M., Sayegh, M. H., Sadée, W., & Frank, M. H. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3327 · Cited by 575 · see citing works
Satyamoorthy, K., Li, G., Gerrero, M. R., Brose, M. S., Volpe, P., Weber, B. L., Belle, P. A. V., Elder, D. E., & Herlyn, M. (2003) · PubMed · Cited by 426 · see citing works
The B-cell receptor signaling pathway as a therapeutic target in CLL
Woyach, J. A., Johnson, A. J., & Byrd, J. C. (2012) · Blood · doi:10.1182/blood-2012-02-362624 · Cited by 412 · see citing works
Eigentler, T., Caroli, U. M., Radny, P., & Garbe, C. (2003) · The Lancet Oncology · doi:10.1016/s1470-2045(03)01280-4 · Cited by 323 · cited 1× · see citing works
“Successful treatment of melanoma is particularly impaired by the fact that metastatic disease quickly becomes resistant to chemotherapy and combination therapies, respectively.(19,20) Two proteins have recently been shown to confer chemoresistance specifically to melanoma cells: the ATP-dependent drug efflux transport…”
BackgroundAasen, T., & Belmonte, J. C. I. (2010) · Nature Protocols · doi:10.1038/nprot.2009.241 · Cited by 318 · see citing works
Dai, D. L., Martinka, M., & Li, G. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.07.168 · Cited by 318 · see citing works
Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma.
Bleehen, N. M., Newlands, E. S., Lee, S. M., Thatcher, N., Selby, P., Calvert, H., Rustin, G. J. S., Brampton, M., & Stevens, M. F. G. (1995) · Journal of Clinical Oncology · doi:10.1200/jco.1995.13.4.910 · Cited by 282 · see citing works
Friedegund, M. (2005) · Frontiers in bioscience · doi:10.2741/1755 · Cited by 265 · see citing works
A Simple Hanging Drop Cell Culture Protocol for Generation of 3D Spheroids
Foty, R. (2011) · Journal of Visualized Experiments · doi:10.3791/2720 · Cited by 263 · cited 1× · see citing works
“Melanoma spheroids were generated via the ‘hanging drop’ method incorporating 250 melanoma cells per 25ml RPMI placed on the lid of a non-adhesive PBS containing petri dish.(15) Spheroids were incubated for 15 days at 371C, 5% CO2.”
MethodFrank, N. Y., Pendse, S. S., Lapchak, P. H., Margaryan, A., Shlain, D., Doeing, C., Sayegh, M. H., & Frank, M. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308700200 · Cited by 242 · see citing works
Human Melanoma Progression in Skin Reconstructs
Meier, F. E., Nesbit, M., Hsu, M., Martin, B. G., Belle, P. A. V., Elder, D. E., Schaumburg‐Lever, G., Garbe, C., Walz, T. M., DONATIEN, P. D., et al. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64719-0 · Cited by 226 · see citing works
Ganten, T. M., Koschny, R., Sykora, J., Schulze‐Bergkamen, H., Büchler, P., Haas, T. L., Schader, M. B., Untergasser, A., Stremmel, W., & Walczak, H. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2635 · Cited by 216 · cited 1× · see citing works
“Recombinant human iz-TRAIL protein was prepared as previously described.(41) Cisplatin was obtained from Platinex (Bristol, UK).”
MethodKeilholz, U., Goey, S. H., Punt, C. J. A., Proebstle, T. M., Salzmann, R., Scheibenbogen, C., Schadendorf, D., Liénard, D., Enk, A., Dummer, R., et al. (1997) · Journal of Clinical Oncology · doi:10.1200/jco.1997.15.7.2579 · Cited by 193 · see citing works
Growth and Cellular Characteristics of Multicell Spheroids
Sutherland, R. M., & Durand, R. E. (1984) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-642-82340-4_2 · Cited by 167 · cited 1× · see citing works
“nodes, micrometastasis or inter-capillary micro regions of solid tumors (Figure 2a).(16,17) We next inserted a defined number of these spheroids (10)”
MethodBasement membranes in skin: unique matrix structures with diverse functions?
Breitkreutz, D., Mirancea, N., & Nischt, R. (2009) · Histochemistry and Cell Biology · doi:10.1007/s00418-009-0586-0 · Cited by 160 · cited 1× · see citing works
“Given the need for better suitable in vitro test systems, we have generated a full thickness organotypic human skin model that displays a differentiation status homologous to normal human skin.(30) Aiming to decode the molecular mechanisms decisive for melanoma resistance, we took advantage of large and differentiated…”
BackgroundMelanoma Stem Cells: The Dark Seed of Melanoma
Zabierowski, S. E., & Herlyn, M. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.5465 · Cited by 157 · cited 1× · see citing works
“This distribution of tumor cell sub-populations is guaranteed by the spheroid sizes, being due to a lack of nutrients and oxygen in the central part where catabolic waste accumulates (Figure 3c).(18) Successful treatment of melanoma is particularly impaired by the fact that metastatic disease quickly becomes resistant…”
BackgroundTreatment for metastatic malignant melanoma: Old drugs and new strategies
Mouawad, R., Sébert, M., Michels, J., Bloch, J., Spano, J., & Khayat, D. (2009) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2009.08.005 · Cited by 123 · cited 1× · see citing works
“Successful treatment of melanoma is particularly impaired by the fact that metastatic disease quickly becomes resistant to chemotherapy and combination therapies, respectively.(19,20) Two proteins have recently been shown to confer chemoresistance specifically to melanoma cells: the ATP-dependent drug efflux transport…”
BackgroundMeier, F. E., Busch, S., Lasithiotakis, K. G., Kulms, D., Garbe, C., Maczey, E., Herlyn, M., & Schittek, B. (2007) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2007.07821.x · Cited by 119 · cited 1× · see citing works
“tools for novel therapeutic approaches, especially 3D models that contain human MM cells.(12) However, most current models are limited to the dermal compartment of the skin that contains MM nests consisting of only few cells and therefore do not adequately recapitulate melanoma metastases.”
BackgroundSmac mimetics as new cancer therapeutics
Chen, D. J., & Huerta, S. (2009) · Anti-Cancer Drugs · doi:10.1097/cad.0b013e32832ced78 · Cited by 113 · see citing works
TRAIL and Other TRAIL Receptor Agonists as Novel Cancer Therapeutics
Falschlehner, C., Ganten, T. M., Koschny, R., Schaefer, U., & Walczak, H. (2009) · Advances in experimental medicine and biology · doi:10.1007/978-0-387-89520-8_14 · Cited by 92 · cited 1× · see citing works
“ment is increasingly seconded by the application of targeted therapeutics, for example, inhibitors of kinases,(32) the proteasome(33) or NF-kB activation,(34) as well as drugs targeting apoptotic pathways, including Smac and BH3 mimetics(35) and agonists of apoptosis-inducing TRAIL receptors.(36) Still, many melanoma…”
BackgroundNguyen, T., Zhang, X. D., & Hersey, P. (2001) · PubMed · Cited by 88 · see citing works
Elder, D. E., Clark, W. H., Elenitsas, R., Guerry, D., & Halpern, A. C. (1993) · PubMed · Cited by 79 · see citing works
RBP2‐H1/JARID1B is a transcriptional regulator with a tumor suppressive potential in melanoma cells
Roesch, A., Mueller, A. M., Stempfl, T., Moehle, C., Landthaler, M., & VOGT, T. M. (2007) · International Journal of Cancer · doi:10.1002/ijc.23211 · Cited by 78 · cited 1× · see citing works
“Two proteins have recently been shown to confer chemoresistance specifically to melanoma cells: the ATP-dependent drug efflux transporter ABCB5(21,22) and JARID1B, a histone H3 demethylase that slows down the cell cycle.(23,24) Comparing the expression levels of ABCB5 and JARID1B in melanoma spheroids with primary cut…”
BackgroundHornle, M., Peters, N., Thayaparasingham, B., Vörsmann, H., Kashkar, H., & Kulms, D. (2010) · Oncogene · doi:10.1038/onc.2010.434 · Cited by 78 · cited 3× · see citing works
“Irradiation with sublethal ultraviolet-B radiation (UVB) synergistically rendered them TRAIL sensitive by a mechanism involving caspase-3dependent cleavage of the X-linked inhibitor of apoptosis protein (XIAP).(13,14) Here, we find a similar, albeit less pronounced cisplatin-mediated TRAIL sensitization of melanoma ce…”
BackgroundInfluentialBortezomib Combination Therapy in Multiple Myeloma
Kapoor, P., Ramakrishnan, V. G., & Rajkumar, S. V. (2012) · Seminars in Hematology · doi:10.1053/j.seminhematol.2012.04.010 · Cited by 77 · see citing works
Belyanskaya, L. L., Marti, T. M., Hopkins-Donaldson, S., Kurtz, S., Felley‐Bosco, E., & Stahel, R. A. (2007) · Molecular Cancer · doi:10.1186/1476-4598-6-66 · Cited by 67 · cited 1× · see citing works
“Furthermore, cisplatin is known to sensitize cancer cells from tissues of various origins to TRAIL-induced apoptosis.(27,28) When used at clinically achievable concentrations, cisplatin sensitized resistant melanoma cells representing the three major progression stages SBCL2 (RGP), WM-115 (VGP) and 451-LU (MM) to TRAI…”
BackgroundStrozyk, E. A., Pöppelmann, B., Schwarz, T., & Kulms, D. (2006) · Oncogene · doi:10.1038/sj.onc.1209655 · Cited by 56 · see citing works
Chen, C.-S. J., Lavker, R. M., Rodeck, U., Risse, B. C., & Jensen, P. J. (1995) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12613595 · Cited by 51 · see citing works
Blanářová, O. V., Jelínková, I., Szöőr, Á., Skender, B., Souček, K., Horváth, V., Vaculová, A. H., Anděra, L., Sova, P., Szöllõsi, J., et al. (2010) · Carcinogenesis · doi:10.1093/carcin/bgq220 · Cited by 41 · see citing works
Satyamoorthy, K., Meier, F. E., Hsu, M., Berking, C., & Herlyn, M. (1999) · Cancer and Metastasis Reviews · doi:10.1023/a:1006333627271 · Cited by 34 · see citing works
Sensitization of melanoma cells to TRAIL by UVB-induced and NF-κB-mediated downregulation of xIAP
Thayaparasingham, B., Kunz, A., Peters, N., & Kulms, D. (2008) · Oncogene · doi:10.1038/onc.2008.397 · Cited by 33 · see citing works
Human cutaneous malignant melanoma as a model for cancer
Clark, W. H. (1991) · Cancer and Metastasis Reviews · doi:10.1007/bf00049406 · Cited by 33 · see citing works
20 Years After – Milestones in Molecular Photobiology
Kulms, D., & Schwarz, T. (2002) · Journal of Investigative Dermatology Symposium Proceedings · doi:10.1046/j.1523-1747.2002.19638.x · Cited by 22 · cited 3× · see citing works
“In a previous monolayer-based study, we showed that 16 out of 18 melanoma cell lines were synergistically sensitized to TRAIL-induced apoptosis by co-application of sublethal UVB radiation.13,14 Primary metastases, however, penetrate into deeper, dermal parts of the skin and secondary metastases invade even further in…”
BackgroundInfluentialRandomized, double‐blind, placebo‐controlled trial of sulindac in individuals at risk for melanoma
Curiel‐Lewandrowski, C. N., Swetter, S. M., Einspahr, J. G., Hsu, C., Nagle, R. B., Sagerman, P. J., Tangrea, J. A., Parnes, H. L., Alberts, D. S., & Chow, H. (2012) · Cancer · doi:10.1002/cncr.27540 · Cited by 21 · see citing works
Screening for malignant melanoma using instant photography
Edmondson, P., Curley, R. K., Marsden, R. A., Robinson, D., Allaway, S. L., & Willson, C. D. (1999) · Journal of Medical Screening · doi:10.1136/jms.6.1.42 · Cited by 21 · cited 1× · see citing works
“Keratinocytes were prepared from the epidermis and fibroblasts form the dermis of juvenile human foreskin,(39) Melanocytes were prepared from adult skin.(40) Keratinocytes were maintained in KGM 2 (PromoCell, Heidelberg, Germany), passaged at 50–70% confluency and used at passage four.”
Method
Flagged first, then by citations
Cited by
Sorted by citations
3D tumor spheroids: an overview on the tools and techniques used for their analysis
Costa, E. C., Moreira, A. F., de Melo-Diogo, D., Gaspar, V. M., Carvalho, M. P., & Correia, I. J. (2016) · Biotechnology Advances · doi:10.1016/j.biotechadv.2016.11.002 · Cited by 929 · see citing works
Matrigel: From discovery and ECM mimicry to assays and models for cancer research
Benton, G., Arnaoutova, I., George, J., Kleinman, H. K., & Koblinski, J. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.06.005 · Cited by 477 · see citing works
Skin models for the testing of transdermal drugs
Abd, E., Yousuf, S. A., Pastore, M. N., Telaprolu, K. C., Mohammed, Y., Namjoshi, S., Grice, J. E., & Roberts, M. S. (2016) · Clinical Pharmacology Advances and Applications · doi:10.2147/cpaa.s64788 · Cited by 418 · see citing works
“Using combination therapies, Vörsmann et al 118 showed significant advantages in using their 3-”
Neutrophil-Derived Proteases Escalate Inflammation through Activation of IL-36 Family Cytokines
Henry, C. M., Sullivan, G. P., Clancy, D. M., Afonina, I. S., Kulms, D., & Martin, S. J. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.072 · Cited by 330 · see citing works
“Active IL-36 Perturbs Differentiation in a 3D Organotypic Skin Model To explore the biological effects of active IL-36 in a more physiologically relevant setting, we utilized a well established model of reconstituted human skin with primary keratinocytes and dermal fibroblasts (Vörsmann et al., 2013).”
MethodThe use of skin models in drug development
Mathes, S. H., Ruffner, H., & Graf‐Hausner, U. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2013.12.006 · Cited by 321 · see citing works
“and UVB or cisplatin [112]”
Fibroblast heterogeneity and its implications for engineering organotypic skin models in vitro
Sriram, G., Bigliardi, P. L., & Bigliardi‐Qi, M. (2015) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2015.08.001 · Cited by 269 · see citing works
Mazuel, F., Espinosa, A., Luciani, N., Reffay, M., Borgne, R. L., Motte, L., Desboeufs, K., Michel, A., Pellegrino, T., Lalatonne, Y., et al. (2016) · ACS Nano · doi:10.1021/acsnano.6b02876 · Cited by 217 · see citing works
3D Bioprinted cancer models: Revolutionizing personalized cancer therapy
Augustine, R., Kalva, S. N., Ahmad, R., Zahid, A. A., Hasan, S., Nayeem, A., McClements, L., & Hasan, A. (2021) · Translational Oncology · doi:10.1016/j.tranon.2021.101015 · Cited by 198 · see citing works
Astashkina, A. I., & Grainger, D. W. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.02.008 · Cited by 194 · see citing works
Advances in the Biofabrication of 3D Skin in vitro: Healthy and Pathological Models
Randall, M. J., Jüngel, A., Rimann, M., & Wuertz‐Kozak, K. (2018) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2018.00154 · Cited by 193 · see citing works
Bioprinting of biomimetic skin containing melanocytes
Min, D., Lee, W., Bae, I., Lee, T. R., Croce, P., & Yoo, S. (2017) · Experimental Dermatology · doi:10.1111/exd.13376 · Cited by 191 · see citing works
Vanderburgh, J. P., Sterling, J. A. R., & Guelcher, S. A. (2016) · Annals of Biomedical Engineering · doi:10.1007/s10439-016-1640-4 · Cited by 184 · see citing works
Kenny, H. A., Lal‐Nag, M., White, E. A., Shen, M., Chiang, C.-Y., Mitra, A. K., Zhang, Y., Curtis, M., Schryver, E. M., Bettis, S., et al. (2015) · Nature Communications · doi:10.1038/ncomms7220 · Cited by 172 · see citing works
Unger, C., Kramer, N., Walzl, A., Scherzer, M., Hengstschläger, M., & Dolznig, H. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.10.015 · Cited by 158 · see citing works
Three-dimensional cancer models mimic cell-matrix interactions in the tumour microenvironment
Herrmann, D., Conway, J. R. W., Vennin, C., Magenau, A., Hughes, W. E., Morton, J. P., & Timpson, P. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu108 · Cited by 141 · see citing works
Construction of 3D multicellular microfluidic chip for an in vitro skin model
Lee, S., Jin, S., Kim, Y. K., Sung, G. Y., Chung, J. H., & Sung, J. H. (2017) · Biomedical Microdevices · doi:10.1007/s10544-017-0156-5 · Cited by 139 · see citing works
Modeling Melanoma In Vitro and In Vivo
Beaumont, K. A., Mohana‐Kumaran, N., & Haass, N. K. (2013) · Healthcare · doi:10.3390/healthcare2010027 · Cited by 112 · see citing works
“Therefore, growing melanoma cells in culture flasks is not always an adequate and reliable system to study melanoma biology and drug resistance [20–22].”
BackgroundA Novel Fully Humanized 3D Skin Equivalent to Model Early Melanoma Invasion
Hill, D. S., Robinson, N. D. P., Caley, M. P., Chen, M., O’Toole, E. A., Armstrong, J. L., Przyborski, S. A., & Lovat, P. E. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0394 · Cited by 106 · see citing works
Embedded Spheroids as Models of the Cancer Microenvironment
Tevis, K. M., Colson, Y. L., & Grinstaff, M. W. (2017) · Advanced Biosystems · doi:10.1002/adbi.201700083 · Cited by 104 · see citing works
Probing the relevance of 3D cancer models in nanomedicine research
Leong, D. T., & Ng, K. W. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.06.007 · Cited by 101 · see citing works
“polymers* [55,117,157]”
BackgroundGencoglu, M. F., Barney, L. E., Hall, C. L., Brooks, E. A., Schwartz, A. D., Corbett, D. C., Stevens, K. R., & Peyton, S. R. (2017) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.7b00069 · Cited by 97 · see citing works
Tissue-engineered 3D melanoma model with blood and lymphatic capillaries for drug development
Bourland, J., Fradette, J., & Auger, F. A. (2018) · Scientific Reports · doi:10.1038/s41598-018-31502-6 · Cited by 94 · see citing works
A novel human leiomyoma tissue derived matrix for cell culture studies
Salo, T. A., Sutinen, M. M., Apu, E. H., Sundquist, E., Cervigne, N. K., de Oliveira, C. E., Akram, S. U., Ohlmeier, S., Suomi, F., Eklund, L., et al. (2015) · BMC Cancer · doi:10.1186/s12885-015-1944-z · Cited by 88 · see citing works
The application of 3D cell models to support drug safety assessment: Opportunities & challenges
Roth, A. B., & Singer, T. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2013.12.005 · Cited by 89 · see citing works
“Today, models are available not only to address effects induced by topical application of cosmetics, for example, but also skin changes arising from topical as well as systemic application of drugs to healthy [86,87] as well as diseased tissue [88].”
Radhakrishnan, J., Varadaraj, S., Dash, S. K., Sharma, A., & Verma, R. S. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.03.002 · Cited by 87 · see citing works
In vitro models for evaluating safety and efficacy of novel technologies for skin drug delivery
Planz, V., Lehr, C., & Windbergs, M. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.09.002 · Cited by 86 · see citing works
Cell Spheroids with Enhanced Aggressiveness to Mimic Human Liver Cancer In Vitro and In Vivo
Jung, H.-R., Kang, H. M., Ryu, J., Kim, D., Noh, K. H., Kim, E., Lee, H., Chung, K., Cho, H., Kim, N.-S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10828-7 · Cited by 82 · see citing works
Human skin models: From healthy to disease-mimetic systems; characteristics and applications
Moniz, T., Costa Lima, S. A., & Reis, S. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15184 · Cited by 80 · see citing works
“SBCL2 (RGP) and WM-115 (VGP) 451-LU (MM) cells, was designed to mimic in vivo tumour environment and showed in vivo-like responses (Vorsmann et al., 2013).”
BackgroundFrom 2D to 3D and beyond: the evolution and impact of in vitro tumor models in cancer research
Rauner, G., Gupta, P. B., & Kuperwasser, C. (2025) · Nature Methods · doi:10.1038/s41592-025-02769-1 · Cited by 73 · see citing works
“This method allows for better nutrient and gas exchange but also mimics certain physiological conditions by exposing part of the organoid to air while maintaining a liquid medium at the base—akin to tissues such as lung, colon, stomach and skin 125–127 .”
Kim, B. S., Cho, W., Gao, G., Ahn, M., Kim, J., & Cho, D. (2021) · Small Methods · doi:10.1002/smtd.202100072 · Cited by 73 · see citing works
Construction of a high fidelity epidermis-on-a-chip for scalable in vitro irritation evaluation
Zhang, J., Chen, Z., Zhang, Y., Wang, X., Ouyang, J., Zhu, J., Yan, Y., Sun, X., Wang, F., Li, X., et al. (2021) · Lab on a Chip · doi:10.1039/d1lc00099c · Cited by 71 · see citing works
Singh, M., Close, D. A., Mukundan, S., Johnston, P. A., & Sant, S. (2015) · Assay and Drug Development Technologies · doi:10.1089/adt.2015.662 · Cited by 69 · see citing works
“It is also known that as a tumor grows in size, it produces differential proliferation zones with proliferating cells at the outer boundary and necrotic/apoptotic cells in the core of the tumor.(32) When 6-day-old small and large microtumors were stained with Ki-67 (marker for proliferating cells) and PI (apoptotic ma…”
Shah, S., & D’Souza, G. G. M. (2025) · Cells · doi:10.3390/cells14100732 · Cited by 66 · see citing works
“In melanoma spheroids, for example, fibroblasts have been shown to accumulate in low-oxygen regions and upregulate genes associated with ECM production and wound response [288].”
In vitro skin three-dimensional models and their applications
Klicks, J., von Molitor, E., Fauth, T., Rudolf, R., & Hafner, M. (2017) · Journal of Cellular Biotechnology · doi:10.3233/jcb-179004 · Cited by 63 · see citing works
“/ In vitro skin three-dimensional models and their applications for biochemical analysis [30].”
BackgroundHaridas, P., McGovern, J., McElwain, S. D., & Simpson, M. J. (2017) · PeerJ · doi:10.7717/peerj.3754 · Cited by 65 · see citing works
Targeting the Complexity of In Vitro Skin Models: A Review of Cutting-Edge Developments
Quílez, C., Bebiano, L. B., Jones, E., Maver, U., Meesters, L., Parzymies, P., Petiot, E., Rikken, G., Risueño, I., Zaidi, H., et al. (2024) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2024.04.032 · Cited by 65 · see citing works
Klicks, J., Maßlo, C., Kluth, M. A., Rudolf, R., & Hafner, M. (2019) · BMC Cancer · doi:10.1186/s12885-019-5606-4 · Cited by 59 · see citing works
Artificial skin models for animal-free testing
Yun, Y. E., Jung, Y. J., Choi, Y. J., Choi, J. S., & Cho, Y. W. (2018) · Journal of Pharmaceutical Investigation · doi:10.1007/s40005-018-0389-1 · Cited by 62 · see citing works
Prasad, M., Kumar, R., Buragohain, L., Kumari, A., & Ghosh, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.696668 · Cited by 62 · see citing works
Impedance Spectroscopy for the Non-Destructive Evaluation of In Vitro Epidermal Models
Groeber, F., Engelhardt, L., Egger, S., Werthmann, H., Monaghan, M. G., Walles, H., & Hansmann, J. (2014) · Pharmaceutical Research · doi:10.1007/s11095-014-1580-3 · Cited by 60 · see citing works
“logical research ranging from melanoma research (6), the assessment of skin corrosion (7,8), skin irritation (9,10), and the penetration of chemical agents (11).”
BackgroundThe Effect of Lycopene Preexposure on UV‐B‐Irradiated Human Keratinocytes
Ascenso, A., Pedrosa, T., Pinho, S., Pinho, F., Oliveira, J. M. P. F. D., Cabral Marques, H., Oliveira, H., Simões, S., & Santos, C. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/8214631 · Cited by 57 · see citing works
Cho, W., Ahn, M., Kim, B. S., & Cho, D. (2022) · Advanced Science · doi:10.1002/advs.202202093 · Cited by 56 · see citing works
Spontaneously-forming spheroids as anin vitrocancer cell model for anticancer drug screening
Theodoraki, M. A., Júnior, C. D. O. R., Chantarasriwong, O., Corben, A. D., Theodorakis, E. A., & Alpaugh, M. L. (2015) · Oncotarget · doi:10.18632/oncotarget.4013 · Cited by 57 · see citing works
Reality Check for Nanomaterial‐Mediated Therapy with 3D Biomimetic Culture Systems
Tay, C. Y., Muthu, M. S., Chia, S. L., Nguyen, K. T., Feng, S., & Leong, D. T. (2016) · Advanced Functional Materials · doi:10.1002/adfm.201600476 · Cited by 54 · see citing works
Roy, V., Magne, B., Vaillancourt-Audet, M., Blais, M., Chabaud, S., Grammond, E., Piquet, L., Fradette, J., Laverdière, I., Moulin, V. J., et al. (2020) · BioMed Research International · doi:10.1155/2020/6051210 · Cited by 53 · see citing works
“Such 3D organotypic skin-bearing melanoma spheroids have been useful to investigate anticancer drugs in an environment that recreates a major part of the complexity of the tumor [186, 188].”
Background3D biofabrication of diseased human skin models in vitro
Ahn, M., Cho, W.-W., Park, W., Lee, J., Choi, M.-J., Gao, Q., Gao, G., Cho, D., & Kim, B. S. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00415-5 · Cited by 53 · see citing works
“Using this model, Vörsmann et al. evaluated the sensitivity of melanoma cells to a tumor necrosis factor-related apoptosis-inducing ligand when ultraviolet B and cisplatin were applied simultaneously [57].”
MethodProgress in melanoma modelling in vitro
Marconi, A., Quadri, M., Saltari, A., & Pincelli, C. (2018) · Experimental Dermatology · doi:10.1111/exd.13670 · Cited by 51 · see citing works
Gupta, S., Maurya, P., Upadhyay, A., Kushwaha, P., Krishna, S., Siddiqi, M. I., Sashidhara, K. V., & Banerjee, D. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.11.015 · Cited by 51 · see citing works
Parhi, R. (2023) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2023.104395 · Cited by 49 · see citing works
Bianchi, A., Wawrzyniak, J. A., Bagati, A., Marvin, E. K., Ackroyd, J. J., Moparthy, S., Bshara, W., Fink, E. E., Foley, C. E., Morozevich, G. E., et al. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2015.47 · Cited by 50 · see citing works
“Melanoma is one of the most aggressive types of human cancers, and its lifetime risk and mortality rates have been steadily increasing for decades.(41,42) In addition, melanomas are exceptionally resistant to chemotherapy treatment and have a high incidence of relapse.”
BackgroundTRAIL-Mediated Apoptosis in Breast Cancer Cells Cultured as 3D Spheroids
Chandrasekaran, S., Marshall, J. R., Messing, J. A., Hsu, J., & King, M. R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111487 · Cited by 49 · see citing works
Immune-competent human skin disease models
Bergers, L. L., Reijnders, C. M. A., van den Broek, L. J., Spiekstra, S. W., de Gruijl, T. D., Weijers, E. M., & Gibbs, S. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.05.008 · Cited by 49 · see citing works
A 3D Organotypic Melanoma Spheroid Skin Model
Müller, I., & Kulms, D. (2018) · Journal of Visualized Experiments · doi:10.3791/57500 · Cited by 49 · see citing works
“This figure has been taken from Voersmann et al.(15) with permission.”
MethodInfluentialOrganotypic 3D Models of the Ovarian Cancer Tumor Microenvironment
Watters, K. M., Bajwa, P., & Kenny, H. A. (2018) · Cancers · doi:10.3390/cancers10080265 · Cited by 49 · see citing works
Non-animal models in dermatological research
Dellambra, E. (2018) · ALTEX · doi:10.14573/altex.1808022 · Cited by 47 · see citing works
Niessner, H., Sinnberg, T., Kosnopfel, C., Smalley, K., Beck, D., Praetorius, C., Mai, M., Beissert, S., Kulms, D., Schaller, M., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0098 · Cited by 42 · see citing works
“Melanoma spheroids were generated and prepared via the "hanging drop" method as described previously (19).”
MethodAnti-Cancer Drug Validation: the Contribution of Tissue Engineered Models
Carvalho, M. R., Lima, D., Reis, R. L., Oliveira, J. M., & Correlo, V. M. (2017) · Stem Cell Reviews and Reports · doi:10.1007/s12015-017-9720-x · Cited by 44 · see citing works
The renaissance of human skin organ culture: A critical reappraisal
Zhou, L., Zhang, X., Paus, R., & Lu, Z. (2018) · Differentiation · doi:10.1016/j.diff.2018.10.002 · Cited by 41 · see citing works
Saltari, A., Truzzi, F., Quadri, M., Lotti, R., Palazzo, E., Grisendi, G., Tiso, N., Marconi, A., & Pincelli, C. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2016.05.116 · Cited by 40 · see citing works
“Skin reconstructs are a good tool for studying tumor-microenvironment interactions (Vo¨rsmann et al., 2013).”
MethodCalcium phosphate nanoparticle-mediated transfection in 2D and 3D mono- and co-culture cell models
Sokolova, V., Rojas‐Sánchez, L., Białas, N., Schulze, N., & Epple, M. (2018) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.11.051 · Cited by 40 · see citing works
Urciuolo, F., Garziano, A., Imparato, G., Panzetta, V., Fusco, S., Casale, C., & Netti, P. A. (2016) · Biofabrication · doi:10.1088/1758-5090/8/1/015010 · Cited by 36 · see citing works
3D melanoma spheroid model for the development of positronium biomarkers
Karimi, H., Moskal, P., Żak, A., & Stępień, E. Ł. (2023) · Scientific Reports · doi:10.1038/s41598-023-34571-4 · Cited by 32 · see citing works
The Melding of Drug Screening Platforms for Melanoma
Couto, G. K., Segatto, N. V., Oliveira, T. L., Seixas, F. K., Schachtschneider, K. M., & Collares, T. V. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00512 · Cited by 34 · see citing works
Full-Thickness Human Skin Equivalent Models of Atopic Dermatitis
Sriram, G., Bigliardi, P. L., & Bigliardi‐Qi, M. (2018) · Methods in molecular biology · doi:10.1007/7651_2018_163 · Cited by 32 · see citing works
Novotný, J., Strnadová, K., Dvořánková, B., Kocourková, Š., Jakša, R., Dundr, P., Pačes, V., Smetana, K., Kolář, M., & Lacina, L. (2020) · Cancers · doi:10.3390/cancers12113324 · Cited by 29 · see citing works
“Data from 3D cultures can more closely mimic the clinical setting, and this justifies their employment [26].”
BackgroundGoncalves, K., Gomez, P. D. L. S., Costello, L., Smith, L. A., Mead, H., Simpson, A., & Przyborski, S. A. (2022) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10415 · Cited by 28 · see citing works
A 3-D cell culture system to study epithelia functions using microcarriers
Jakob, P., Kehrer, J., Flood, P. F., Wiegel, C., Haselmann, U., Meissner, M., Stelzer, E. H. K., & Reynaud, E. G. (2016) · Cytotechnology · doi:10.1007/s10616-015-9935-0 · Cited by 27 · see citing works
“However, cysts are closed structures with an internalized lumen that do not allow access to the apical membrane for manipulation (infection, transfection and microinjection), and spheroids are disorganized cell aggregates that lack the structure necessary to mimic healthy in vivo tissue (Vörsmann et al. 2013).”
Advances in, and prospects of, 3D preclinical models for skin drug discovery
Imran, M., Moyle, P. M., Kamato, D., & Mohammed, Y. (2024) · Drug Discovery Today · doi:10.1016/j.drudis.2024.104208 · Cited by 27 · see citing works
In Vitro Three-Dimensional (3D) Models for Melanoma Immunotherapy
Nomdedeu‐Sancho, G., Gorkun, A. A., Mahajan, N., Willson, K., Schaaf, C. R., Votanopoulos, K. I., Atala, A., & Söker, S. (2023) · Cancers · doi:10.3390/cancers15245779 · Cited by 25 · see citing works
“Because the primary biopsy of melanoma is heterogeneous and contains different cell types, the addition of the melanoma cells into the hPSkCs as pre-assembled multicellular tumor organoids can standardize the contribution of each cell type to the model [24,25].”
BackgroundOsrodek, M., Hartman, M. L., & Czyż, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20174203 · Cited by 25 · see citing works
“These include three-dimensional matrices [1,2], co-cultures with other cell types [3,4] and modifications of culture media supplementation [5–8].”
Developing strategies to predict photodynamic therapy outcome: the role of melanoma microenvironment
Vera, R. E., Lamberti, M. J., Rivarola, V. A., & Vittar, N. B. R. (2015) · Tumor Biology · doi:10.1007/s13277-015-4059-x · Cited by 25 · see citing works
Melanocytes in regenerative medicine applications and disease modeling
Coutant, K., Magne, B., Ferland, K., Fuentes-Rodriguez, A., Chancy, O., Mitchell, A., Germain, L., & Landreville, S. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05113-x · Cited by 24 · see citing works
“In their study, Vörs-mann and colleagues used both reconstructed skin and spheroids made with melanoma cell lines with different genetic backgrounds to recreate the melanoma microenvironment [165].”
BackgroundInfluentialCulturing Uveal Melanoma Cells
Angi, M., Versluis, M., & Kalirai, H. (2015) · Ocular Oncology and Pathology · doi:10.1159/000370150 · Cited by 24 · see citing works
Li, M., Song, X., Jin, S., & Ye, K. (2021) · Bio-Design and Manufacturing · doi:10.1007/s42242-021-00134-7 · Cited by 24 · see citing works
3D Bioprinting: An Enabling Technology to Understand Melanoma
Fernandes, S., Vyas, C., Lim, P., Pereira, R. F., Virós, A., & Bártolo, P. (2022) · Cancers · doi:10.3390/cancers14143535 · Cited by 24 · see citing works
Herrera-Martínez, A. D., van den Dungen, R., Dogan, F., van Koetsveld, P. M., Culler, M. D., de Herder, W. W., Luque, R. M., Feelders, R. A., & Hofland, L. J. (2019) · Endocrine Related Cancer · doi:10.1530/erc-19-0086 · Cited by 23 · see citing works
Animals Used in Research and Education, 1966–2016: Evolving Attitudes, Policies, and Relationships
Lairmore, M. D., & Ilkiw, J. E. (2015) · Journal of Veterinary Medical Education · doi:10.3138/jvme.0615-087r · Cited by 23 · see citing works
Vetma, V., Guttà, C., Peters, N., Praetorius, C., Hutt, M., Seifert, O., Meier, F. E., Kontermann, R. E., Kulms, D., & Rehm, M. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-0512-5 · Cited by 22 · see citing works
Srisongkram, T., Weerapreeyakul, N., & Thumanu, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21114141 · Cited by 23 · see citing works
“The 3D melanoma culture system was introduced in three different ways, including (i) multicellular melanoma spheroids, multicellular melanoma spheroids in skin equivalent model [29], and skin or melanoma on chip [30].”
MethodMelanoma spheroid-containing artificial dermis as an alternative approach to in vivo models
Mônico, D. A., Calori, I. R., Souza, C., Espreáfico, E. M., Bi, H., & Tedesco, A. C. (2022) · Experimental Cell Research · doi:10.1016/j.yexcr.2022.113207 · Cited by 21 · see citing works
A scaffold-free surface culture of B16F10 murine melanoma cells based on magnetic levitation
Jeong, Y. G., Lee, J. S., Shim, J. K., & Hur, W. (2016) · Cytotechnology · doi:10.1007/s10616-016-0026-7 · Cited by 19 · see citing works
“2005) and to construct an organotypic skin melanoma model for in vitro drug testing (Vörsmann et al. 2013).”
MethodTowards an advanced cell-based in vitro glioma model system
Mikhailova, V., Gulaia, V. S., Tiasto, V., Александрович, Р. С., Yatsunskaya, M., & Kagansky, A. (2018) · Global Medical Genetics · doi:10.3934/genet.2018.2.91 · Cited by 18 · see citing works
From simplicity to complexity in current melanoma models
Michielon, E., de Gruijl, T. D., & Gibbs, S. (2022) · Experimental Dermatology · doi:10.1111/exd.14675 · Cited by 16 · see citing works
Michielon, E., González, M. L., Stolk, D. A., Stolwijk, J. G. C., Roffel, S., Waaijman, T., Lougheed, S. M., de Gruijl, T. D., & Gibbs, S. (2023) · Cancers · doi:10.3390/cancers15102849 · Cited by 17 · see citing works
Computational models of melanoma
Albrecht, M., Lucarelli, P., Kulms, D., & Sauter, T. (2020) · Theoretical Biology and Medical Modelling · doi:10.1186/s12976-020-00126-7 · Cited by 17 · see citing works
“Fully functional organotypic skin constructs [123] can mimic all melanoma progression stages.”
BackgroundBridging scales in cancer progression: Mapping genotype to phenotype using neural networks
Gerlee, P., Kim, E., & Anderson, A. R. A. (2014) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2014.04.013 · Cited by 17 · see citing works
“with the development of organotypic cultures that represent a caricature of the real system containing not only cancer cells but also stromal cells (51, 52, 53) and ex vivo assays (54, 55) that can keep a slice of real tissue alive for some time.”
BackgroundLange, J., Weil, F., Riegler, C., Groeber, F., Rebhan, S., Kurdyn, S., Alb, M., Kneitz, H., Gelbrich, G., Walles, H., et al. (2016) · Biotechnology Journal · doi:10.1002/biot.201600360 · Cited by 16 · see citing works
“Currently, artificial human skin models are used as a test platform for cosmetic, pharmacological, immunological, pathological and microbiological in vitro studies [2-5].”
BackgroundMistro, G. D., Riemann, S., Schindler, S., Beissert, S., Kontermann, R. E., Ginolhac, A., Halder, R., Presta, L., Sinkkonen, L., Sauter, T., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04502-8 · Cited by 15 · see citing works
“3D melanoma spheroids Melanoma spheroids were generated using the “hanging drop” method [24].”
BackgroundMethodA preclinical model of cutaneous melanoma based on reconstructed human epidermis
Leikeim, A., Wußmann, M., Schmidt, F. F., Neto, N. G. B., Benz, F., Tiltmann, K., Junger, C., Monaghan, M. G., Schilling, B., & Groeber-Becker, F. K. (2022) · Scientific Reports · doi:10.1038/s41598-022-19307-0 · Cited by 15 · see citing works
Chen, H., Wei, X., Chen, H., Wei, H., Wang, Y., Nan, W., Zhang, Q., & Wen, X. (2019) · Artificial Cells Nanomedicine and Biotechnology · doi:10.1080/21691401.2018.1544142 · Cited by 15 · see citing works
Generation of 3D melanoma models using an assembloid-based approach
Rodrigues, D. B., Moreira, H. R., Jarnalo, M., Horta, R., Marques, A. P., Reis, R. L., & Pirraco, R. P. (2024) · Acta Biomaterialia · doi:10.1016/j.actbio.2024.02.023 · Cited by 14 · see citing works
ReBiA—Robotic Enabled Biological Automation: 3D Epithelial Tissue Production
Königer, L., Malkmus, C., Mahdy, D., Däullary, T., Götz, S., Schwarz, T., Gensler, M., Pallmann, N., Cheufou, D. H., Rosenwald, A., et al. (2024) · Advanced Science · doi:10.1002/advs.202406608 · Cited by 14 · see citing works
Fucina, G., Cesca, K., Berti, F. V., Biavatti, M. W., & Porto, L. M. (2022) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2022.130183 · Cited by 13 · see citing works
Characterization of human melanoma skin cancer models: A step towards model-based melanoma research
Daugaard, N. D., Tholstrup, R., Tornby, J. R., Bendixen, S. M., Larsen, F. T., Zio, D. D., Barnkob, M. B., Ravnskjær, K., & Brewer, J. R. (2024) · Acta Biomaterialia · doi:10.1016/j.actbio.2024.11.018 · Cited by 13 · see citing works
Modeling Skin Inflammation Using Human In Vitro Models
Boarder, E., Rumberger, B., & Howell, M. D. (2021) · Current Protocols · doi:10.1002/cpz1.72 · Cited by 12 · see citing works
Commandeur, S., SPARKS, S. J., Chan, H. L., Gao, L. Y., Out‐Luiting, J. J., Gruis, N. A., van Doorn, R., & Ghalbzouri, A. E. (2014) · Melanoma Research · doi:10.1097/cmr.0000000000000079 · Cited by 13 · see citing works
Liposomal fusion of plant-based extracellular vesicles to enhance skin anti-inflammation
Ryu, J. S., Park, H. S., Kim, M. J., Lee, J.-S., Jeong, E. Y., Cho, H., Kim, S., Seo, J. Y., Cho, H. D., Kang, H. C., et al. (2024) · Journal of Industrial and Engineering Chemistry · doi:10.1016/j.jiec.2024.09.038 · Cited by 12 · see citing works
Recreating Human Skin In Vitro: Should the Microbiota Be Taken into Account?
Galvan, A., Pellicciari, C., & Calderan, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021165 · Cited by 11 · see citing works
Kaczmarek, K., Wieckiewicz, J., Węglarczyk, K., Siedlar, M., & Baran, J. (2021) · Cancers · doi:10.3390/cancers13123004 · Cited by 11 · see citing works
“showed resistance of melanoma cell spheroids to TRAIL, while the same cells grown in a monolayer were sensitive to TRAIL-induced apoptosis [63].”
BackgroundAngeli, C., Wróblewska, J. P., Klein, E., Margue, C., & Kreis, S. (2024) · STAR Protocols · doi:10.1016/j.xpro.2024.103058 · Cited by 10 · see citing works
- Authors
- Vörsmann, H., Groeber, F., Walles, H., Busch, S., Beissert, S., Walczak, H., & Kulms, D.
- Affiliations
- University of Stuttgart (DE)
- Fraunhofer Institute for Interfacial Engineering and Biotechnology (DE)
- Technische Universität Dresden (DE)
- University College London (GB)
- Corresponding author
- Kulms, D
- Venue
- Cell Death & Disease
- Published
- 2013-07-11
- Volume
- 4
- Issue
- 7
- Pages
- e719-e719
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC3730422
- OpenAlex
- W2042222655
- Cited by
- 168
- References
- 44
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 14 · 2023: 8 · 2022: 18 · 2021: 12 · 2020: 15 · 2019: 14 · 2018: 16 · 2017: 14 · 2016: 16 · 2015: 13 · 2014: 11 · 2013: 1
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Cell Death and Disease (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- Funders
- Deutsche Krebshilfe
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Keywords
- metastatic melanoma, 3D tumor models, TRAIL sensitization, cisplatin, UV-B radiation, combination therapy, drug resistance, in vitro drug testing, tumor necrosis factor-related apoptosis-inducing ligand
- MeSH terms
- Antineoplastic Agents, Cisplatin, Drug Screening Assays, Antitumor, Drug Synergism, Humans, Melanoma, Skin Neoplasms, Skin, Artificial, Spheroids, Cellular, Coculture Techniques, Cell Line, Tumor, TNF-Related Apoptosis-Inducing Ligand
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
