Differentiation States of Phenotypic Transition of Melanoma Cells Are Revealed by 3D Cell Cultures
Open accessAbstract
Melanoma is characterized by high metastatic potential favored by the epithelial-to-mesenchymal transition (EMT), leading melanoma cells to exhibit a spectrum of typical EMT markers. This study aimed to analyze the expression of EMT markers in A375 and BLM melanoma cell lines cultured in 2D monolayers and 3D spheroids using morphological and molecular methods. The expression of EMT markers was strongly affected by 3D arrangement and revealed a hybrid phenotype for the two cell lines. Indeed, although E-cadherin was almost undetectable in both A375 and BLM cells, cortical actin was detected in A375 2D monolayers and 3D spheroids and was strongly expressed in BLM 3D spheroids. The mesenchymal marker N-cadherin was significantly up-regulated in A375 3D spheroids while undetectable in BLM cells, but vimentin was similarly expressed in both cell lines at the gene and protein levels. This pattern suggests that A375 cells exhibit a more undifferentiated/mesenchymal phenotype, while BLM cells have more melanocytic/differentiated characteristics. Accordingly, the Zeb1 and 2, Slug, Snail and Twist gene expression analyses showed that they were differentially expressed in 2D monolayers compared to 3D spheroids, supporting this view. Furthermore, A375 cells are characterized by a greater invasive potential, strongly influenced by 3D arrangement, compared to the BLM cell line, as evaluated by SDS-zymography and TIMPs gene expression analysis. Finally, TGF-β1, a master controller of EMT, and lysyl oxidase (LOX), involved in melanoma progression, were strongly up-regulated by 3D arrangement in the metastatic BLM cells alone, likely playing a role in the metastatic phases of melanoma progression. Overall, these findings suggest that A375 and BLM cells possess a hybrid/intermediate phenotype in relation to the expression of EMT markers. The former is characterized by a more mesenchymal/undifferentiated phenotype, while the latter shows a more melanocytic/differentiated phenotype. Our results contribute to the characterization of the role of EMT in melanoma cells and confirm that a 3D cell culture model could provide deeper insight into our understanding of the biology of melanoma.
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 cells, gene expression remained largely unchanged between monolayer and monolayer-with-ECM conditions, while spheroid cultures exhibited substantial differences.
“transcriptomic analysis of melanoma cells cultured as monolayers, monolayers with ECM, and spheroids revealed that gene expression remained largely unchanged between the two monolayer conditions, while spheroid cultures exhibited substantial differences [194,195].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [195]
The Results (section 3.4; page unavailable) report differences in selected gene-expression markers between 2D monolayers and 3D spheroids. The Cell Cultures methods (section 2.1; page unavailable) describe those two conditions, but no monolayer-with-ECM condition; the paper therefore does not support the claimed comparison between the two monolayer conditions or characterize its analysis as transcriptomic. (LLM, conf=0.88)
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
Siegel, R. L., Miller, K. D., Wagle, N. S., & Jemal, A. (2023) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21763 · Cited by 16,303 · see citing works
The basics of epithelial-mesenchymal transition
Kalluri, R., & Weinberg, R. A. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39104 · Cited by 10,196 · see citing works
Epithelial-Mesenchymal Transitions in Development and Disease
Thiery, J. P., Acloque, H., Huang, R. Y. J., & Nieto, M. A. (2009) · Cell · doi:10.1016/j.cell.2009.11.007 · Cited by 9,931 · see citing works
Molecular mechanisms of epithelial–mesenchymal transition
Lamouille, S., Xu, J., & Derynck, R. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3758 · Cited by 8,091 · see citing works
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Tirosh, I., Izar, B., Prakadan, S. M., Wadsworth, M. H., Treacy, D., Trombetta, J. J., Rotem, A., Rodman, C., Lian, C., Murphy, G., et al. (2016) · Science · doi:10.1126/science.aad0501 · Cited by 4,944 · see citing works
Cano, A., Pérez‐Moreno, M., Rodrigo, I., Locascio, A., Blanco, M. J., Barrio, M. G. D., Portillo, F., & Nieto, M. A. (2000) · Nature Cell Biology · doi:10.1038/35000025 · Cited by 3,672 · see citing works
Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis
Bergers, G., Brekken, R., McMahon, G., Vu, T. H., Itoh, T., Tamaki, K., Tanzawa, K., Thorpe, P., Itohara, S., Werb, Z., et al. (2000) · Nature Cell Biology · doi:10.1038/35036374 · Cited by 2,797 · see citing works
Batlle, E., Sancho, E., Francı́, C., Dominguez-Sola, D., Monfar, M., Baulida, J., & de Herreros, A. G. (2000) · Nature Cell Biology · doi:10.1038/35000034 · Cited by 2,671 · see citing works
Biomarkers for epithelial-mesenchymal transitions
Zeisberg, M., & Neilson, E. G. (2009) · Journal of Clinical Investigation · doi:10.1172/jci36183 · Cited by 2,299 · cited 2× · see citing works
“Although, during EMT, a complete conversion of epithelial into mesenchymal cells can occur, cancer cells often undergo an incomplete or partial EMT, resulting in the acquisition of a hybrid phenotype with the concomitant expression of both epithelial and mesenchymal markers [7,8].”
BackgroundBrabletz, T., Kalluri, R., Nieto, M. A., & Weinberg, R. A. (2018) · Nature Reviews Cancer · doi:10.1038/nrc.2017.118 · Cited by 1,961 · see citing works
Mechanism Of Cell Surface Activation Of 72-kDa Type IV Collagenase
Strongin, A. Y., Collier, I. E., Bannikov, G. A., Marmer, B. L., Grant, G. A., & Goldberg, G. I. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.10.5331 · Cited by 1,589 · see citing works
Tissue inhibitors of metalloproteinases: structure, regulation and biological functions.
Gomez, D. E., Alonso, D. F., Yoshiji, H., & Thorgeirsson, U. P. (1997) · PubMed · Cited by 1,508 · see citing works
Loh, C.-Y., Chai, J., Tang, T. F., Wong, W. F., Sethi, G., Shanmugam, M. K., Chong, P. P., & Looi, C. Y. (2019) · Cells · doi:10.3390/cells8101118 · Cited by 1,323 · see citing works
The Genetic Evolution of Melanoma from Precursor Lesions
Shain, A. H., Yeh, I., Kovalyshyn, I., Sriharan, A., Talevich, E., Gagnon, A., Dummer, R., North, J. P., Pincus, L. B., Ruben, B. S., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1502583 · Cited by 1,065 · see citing works
The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis
Huang, Y., Hong, W., & Wei, X. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01347-8 · Cited by 1,065 · see citing works
Epithelial to Mesenchymal Transition in Renal Fibrogenesis
Liu, Y. (2004) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000106015.29070.e7 · Cited by 1,054 · see citing works
Oncogenic roles of EMT-inducing transcription factors
Puisieux, A., Brabletz, T., & Caramel, J. (2014) · Nature Cell Biology · doi:10.1038/ncb2976 · Cited by 1,032 · see citing works
Regulation of the Polarity Protein Par6 by TGFß Receptors Controls Epithelial Cell Plasticity
Ozdamar, B., Bose, R., Barrios-Rodiles, M., Wang, H.-R., Zhang, Y., & Wrana, J. L. (2005) · Science · doi:10.1126/science.1105718 · Cited by 881 · see citing works
<i>In vivo</i> Switching of Human Melanoma Cells between Proliferative and Invasive States
Hoek, K. S., Eichhoff, O. M., Schlegel, N. C., Döbbeling, U., Kobert, N., Schaerer, L., Hemmi, S., & Dummer, R. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-2491 · Cited by 743 · see citing works
Cutaneous melanoma: From pathogenesis to therapy (Review)
Leonardi, G. C., Falzone, L., Salemi, R., Zanghì, A., Spandidos, D. A., McCubrey, J. A., Candido, S., & Libra, M. (2018) · International Journal of Oncology · doi:10.3892/ijo.2018.4287 · Cited by 594 · see citing works
Butler, G. S., Butler, M. J., Atkinson, S. J., Will, H., Tamura, T., van Westrum, S. M. S., Crabbe, T., Clements, J. M., d’Ortho, M., & Murphy, G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.2.871 · Cited by 573 · see citing works
A Switch in the Expression of Embryonic EMT-Inducers Drives the Development of Malignant Melanoma
Caramel, J., Papadogeorgakis, E., Hill, L., Browne, G. J., Richard, G., Wierinckx, A., Saldanha, G. S., Osborne, J. E., Hutchinson, P. J., Tse, G., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.08.018 · Cited by 516 · see citing works
TIMPs: versatile extracellular regulators in cancer
Jackson, H. W., Defamie, V., Waterhouse, P. D., & Khokha, R. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.115 · Cited by 454 · see citing works
Matrix Metalloproteinases in Human Melanoma
Hofmann, U. B., Westphal, J. R., van Muijen, G. N. P., et al. (2000) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2000.00068.x · Cited by 428 · see citing works
Epidemiology and Risk Factors of Melanoma
Carr, S. A., Smith, C., & Wernberg, J. A. (2019) · Surgical Clinics of North America · doi:10.1016/j.suc.2019.09.005 · Cited by 362 · see citing works
Alonso, S. R., Tracey, L., Ortiz-Romero, P. L., Pérez‐Gómez, B., Palacios, J., Pollán, M., Linares, J., Serrano, S., Sáez-Castillo, A. I., Sánchez, L., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3481 · Cited by 327 · see citing works
Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunitiesPreprint
Rambow, F., Marine, J., & Goding, C. R. (2019) · Genes & Development · doi:10.1101/gad.329771.119 · Cited by 316 · see citing works
Poser, I., Dominguez-Sola, D., de Herreros, A. G., Varnai, A., Buettner, R., & Bosserhoff, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011224200 · Cited by 280 · see citing works
Nieto, M. A., & Cano, A. (2012) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2012.05.003 · Cited by 263 · see citing works
A cellular hierarchy in melanoma uncouples growth and metastasis
Karras, P., Bordeu, I., Poźniak, J., Nowosad, A., Pazzi, C., Raemdonck, N. V., Landeloos, E., Herck, Y. V., Pedri, D., Bervoets, G., et al. (2022) · Nature · doi:10.1038/s41586-022-05242-7 · Cited by 251 · see citing works
Context specificity of the EMT transcriptional response
Cook, D. P., & Vanderhyden, B. C. (2020) · Nature Communications · doi:10.1038/s41467-020-16066-2 · Cited by 231 · see citing works
TGF β Signaling in Tumor Initiation, Epithelial-to-Mesenchymal Transition, and Metastasis
Papageorgis, P. (2015) · Journal of Oncology · doi:10.1155/2015/587193 · Cited by 224 · see citing works
Dijkstra, G. D. H., Moshage, H. J., van Dullemen, H. M., de Jager-Krikken, A., Tiebosch, A. T. M. G., Kleibeuker, J. H., Jansen, P. L. M., & van Goor, H. (1998) · The Journal of Pathology · doi:10.1002/(sici)1096-9896(199812)186:4 · Cited by 223 · see citing works
Multicellular tumor spheroids: intermediates between monolayer culture and in vivo tumor
Kunz‐Schughart, L. A. (1999) · Cell Biology International · doi:10.1006/cbir.1999.0384 · Cited by 217 · see citing works
Li, G., Schaider, H., Satyamoorthy, K., Hanakawa, Y., Hashimoto, K., & Herlyn, M. (2001) · Oncogene · doi:10.1038/sj.onc.1205034 · Cited by 212 · see citing works
Denecker, G., Vandamme, N., Akay, Ö., Koludrović, D., Taminau, J., Lemeire, K., Gheldof, A., Craene, B. D., Gele, M. V., Brochez, L., et al. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2014.44 · Cited by 203 · see citing works
The journey from melanocytes to melanoma
Centeno, P. P., Pavet, V., & Marais, R. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00565-7 · Cited by 202 · see citing works
Sethi, A., Mao, W., Wordinger, R. J., et al. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.11-7287 · Cited by 196 · see citing works
Heterogeneous Tumor Subpopulations Cooperate to Drive Invasion
Chapman, A., del Ama, L. F., Ferguson, J., Kamarashev, J. A., Wellbrock, C., & Hurlstone, A. F. L. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.06.045 · Cited by 195 · see citing works
Qi, J., Chen, N., Wang, J., & Siu, C. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-03-0186 · Cited by 190 · see citing works
Hsu, M., Andl, T., Li, G., et al. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.9.1535 · Cited by 190 · see citing works
Tı́már, J., & Ladányi, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105384 · Cited by 185 · see citing works
Hendrix, M. J. C., Seftor, E. A., Chu, Y.-W., et al. (1992) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/84.3.165 · Cited by 177 · see citing works
NRAS mutant melanoma: biological behavior and future strategies for therapeutic management
Fedorenko, I. V., Gibney, G. T., & Smalley, K. S. M. (2012) · Oncogene · doi:10.1038/onc.2012.453 · Cited by 171 · see citing works
Potential therapeutic targets of epithelial–mesenchymal transition in melanoma
Pearlman, R. L., de Oca, M. K. M., Pal, H. C., & Afaq, F. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.01.029 · Cited by 164 · see citing works
Wels, C., Joshi, S., Heidinger, P., et al. (2011) · Journal of Investigative Dermatology · doi:10.1038/jid.2011.142 · Cited by 160 · see citing works
van den Oord, J. J., Paemen, L. R., Opdenakker, G., et al. (1997) · PubMed · Cited by 144 · see citing works
Functional Roles of Matrix Metalloproteinases and Their Inhibitors in Melanoma
Napoli, S., Scuderi, C., Gattuso, G., Bella, V. D., Candido, S., Basile, M. S., Libra, M., & Falzone, L. (2020) · Cells · doi:10.3390/cells9051151 · Cited by 142 · see citing works
Sanders, D., Blessing, K., Hassan, G. A., et al. (1999) · Molecular Pathology · doi:10.1136/mp.52.3.151 · Cited by 140 · see citing works
The University of North Carolina at Chapel Hill University Libraries (2020) · PubMed · doi:10.17615/pzdj-d090 · Cited by 137 · see citing works
Smeets, T. J. M., Dolhain, R. J. E. M., Breedveld, F. C., & Tak, P. P. (1998) · The Journal of Pathology · doi:10.1002/(sici)1096-9896(199809)186:1 · Cited by 136 · see citing works
Human melanocyte development and melanoma dedifferentiation at single-cell resolution
Belote, R. L., Le, D., Maynard, A., Lang, U. E., Sinclair, A. W., Lohman, B. K., Planells-Palop, V., Baskin, L. S., Tward, A. D., Darmanis, S., et al. (2021) · Nature Cell Biology · doi:10.1038/s41556-021-00740-8 · Cited by 135 · see citing works
Harane, S. E., Zidi, B., Harane, N. E., Krause, K., Matthes, T., & Preynat‐Seauve, O. (2023) · Cells · doi:10.3390/cells12071001 · Cited by 132 · see citing works
TGF-β-Induced Transcription Sustains Amoeboid Melanoma Migration and Dissemination
Cantelli, G., Orgaz, J. L., Rodríguez‐Hernández, I., Karagiannis, P., Maiques, Ó., Matías‐Guiu, X., Nestle, F. O., Marti, R. M., Karagiannis, S. N., & Sanz‐Moreno, V. (2015) · Current Biology · doi:10.1016/j.cub.2015.09.054 · Cited by 126 · see citing works
Epithelial‐to‐mesenchymal‐like transition events in melanoma
Pedri, D., Karras, P., Landeloos, E., Marine, J., & Rambow, F. (2021) · FEBS Journal · doi:10.1111/febs.16021 · Cited by 126 · see citing works
E-cadherin expression in human melanoma
Danen, E. H. J., de Vries, T. J., Morandini, R., Ghanem, G., Ruiter, D. J., & van Muijen, G. (1996) · Melanoma Research · doi:10.1097/00008390-199604000-00007 · Cited by 117 · see citing works
LOX Expression and Functional Analysis in Astrocytomas and Impact of IDH1 Mutation
da Silva, R., Uno, M., Marie, S. K. N., & Oba‐Shinjo, S. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0119781 · Cited by 110 · see citing works
In vitro 3d cultures to model the tumor microenvironment
Fontana, F., Marzagalli, M., Sommariva, M., Gagliano, N., & Limonta, P. (2021) · Cancers · doi:10.3390/cancers13122970 · Cited by 103 · see citing works
Self-citationLi, M., Zhang, B., Sun, B., Wang, X., Ban, X., Sun, T., Liu, Z., & Zhao, X. (2010) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-29-109 · Cited by 96 · see citing works
Tang, Y., Durand, S., Dalle, S., & Caramel, J. (2020) · Cancers · doi:10.3390/cancers12082154 · Cited by 96 · see citing works
3D cancer models: One step closer to in vitro human studies
Manduca, N., Maccafeo, E., Maria, R. D., Sistigu, A., & Musella, M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1175503 · Cited by 95 · see citing works
NF-κB inhibition is associated with OPN/MMP-9 downregulation in cutaneous melanoma
Guarneri, C., Bevelacqua, V., Polesel, J., Falzone, L., Cannavó, P. S., Spandidos, D. A., Malaponte, G., & Libra, M. (2017) · Oncology Reports · doi:10.3892/or.2017.5362 · Cited by 88 · see citing works
Vandamme, N., Denecker, G., Bruneel, K., Blancke, G., Akay, Ö., Taminau, J., Coninck, J. D., Smedt, E. D., Skrypek, N., Loocke, W. V., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-2373 · Cited by 87 · see citing works
Melanoma Cells Revive an Embryonic Transcriptional Network to Dictate Phenotypic Heterogeneity
Vandamme, N., & Berx, G. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00352 · Cited by 77 · see citing works
Slug Expression during Melanoma Progression
Shirley, S. H., Greene, V. R., Duncan, L. M., Torres-Cabala, C. A., Grimm, E. A., & Kusewitt, D. F. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.02.014 · Cited by 75 · see citing works
Ennen, M., Keime, C., Gambi, G., Kieny, A., Coassolo, S., Thibault-Carpentier, C., Margerin-Schaller, F., Davidson, G., Vagne, C., Lipsker, D. M., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0010 · Cited by 73 · see citing works
Kim, J. E., Leung, E. Y., Baguley, B. C., & Finlay, G. J. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00097 · Cited by 72 · see citing works
Epithelial-Mesenchymal Transition in Skin Cancers: A Review
Hodorogea, A., Călinescu, A., Antohe, M., Balaban, M., Nedelcu, R., Turcu, G., Ion, D. A., Bădărău, I. A., Popescu, C. M., Popescu, R. A., et al. (2019) · Analytical Cellular Pathology · doi:10.1155/2019/3851576 · Cited by 71 · see citing works
Lade‐Keller, J., Riber‐Hansen, R., Guldberg, P., et al. (2013) · British Journal of Dermatology · doi:10.1111/bjd.12426 · Cited by 68 · see citing works
Krengel, S., Grotelüschen, F., Bartsch, S., et al. (2003) · Journal of Cutaneous Pathology · doi:10.1046/j.0303-6987.2004.0106.x · Cited by 65 · see citing works
Lysyl Oxidase Family Proteins: Prospective Therapeutic Targets in Cancer
Wang, W., Wang, X., Yao, F., & Huang, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012270 · Cited by 63 · see citing works
Fontana, F., Raimondi, M., Marzagalli, M., et al. (2019) · Cells · doi:10.3390/cells8020143 · Cited by 62 · see citing works
Self-citationRethinking the biology of metastatic melanoma: a holistic approach
Vandyck, H. H., Hillen, L. M., Bosisio, F. M., van den Oord, J., Hausen, A. Z., & Winnepenninckx, V. J. L. (2021) · Cancer and Metastasis Reviews · doi:10.1007/s10555-021-09960-8 · Cited by 60 · see citing works
Three-Dimensional Cell Cultures as an In Vitro Tool for Prostate Cancer Modeling and Drug Discovery
Fontana, F., Raimondi, M., Marzagalli, M., Sommariva, M., Gagliano, N., & Limonta, P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186806 · Cited by 56 · see citing works
Self-citationNguyen, T., & Mège, R. (2016) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2016.05.002 · Cited by 53 · see citing works
Rictor regulates the vasculogenic mimicry of melanoma via the AKT ‐ MMP ‐2/9 pathway
Liang, X., Sun, R., Zhao, X., et al. (2017) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13268 · Cited by 44 · see citing works
Cheng, Q., Wu, J., Zhang, Y., et al. (2017) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2017.3030 · Cited by 38 · see citing works
Gagliano, N. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i18.4466 · Cited by 37 · see citing works
Self-citationTumor genetic heterogeneity analysis of chronic sun‐damaged melanoma
Sanna, A. M., Harbst, K., Johansson, I., Christensen, G. B., Lauss, M., Mitra, S., Rosengren, F., Häkkinen, J., Vallon‐Christersson, J., Olsson, H. L., et al. (2019) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12851 · Cited by 34 · see citing works
Murtas, D., Maxia, C., Diana, A., et al. (2017) · Histochemistry and Cell Biology · doi:10.1007/s00418-017-1606-0 · Cited by 27 · see citing works
Tumor Organoid and Spheroid Models for Cervical Cancer
Kutle, I., Polten, R., Hachenberg, J., Klapdor, R., Morgan, M. A., & Schambach, A. (2023) · Cancers · doi:10.3390/cancers15092518 · Cited by 27 · see citing works
Chuang, K., Chiou, S., & Hsu, S. (2023) · Cancers · doi:10.3390/cancers15133338 · Cited by 26 · see citing works
STAM-binding protein regulates melanoma metastasis through SLUG stabilization
Iwakami, Y., Yokoyama, S., Watanabe, K., & Hayakawa, Y. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.11.068 · Cited by 25 · see citing works
Sun, J., & Stetler‐Stevenson, W. G. (2009) · Journal of Molecular Signaling · doi:10.1186/1750-2187-4-4 · Cited by 24 · see citing works
Loxl3 Promotes Melanoma Progression and Dissemination Influencing Cell Plasticity and Survival
Vázquez-Naharro, A., Bustos-Tauler, J., Floristán, A., et al. (2022) · Cancers · doi:10.3390/cancers14051200 · Cited by 24 · see citing works
Kharbili, M. E., Cario, M., Béchetoille, N., et al. (2020) · Cancers · doi:10.3390/cancers12051297 · Cited by 23 · see citing works
Ohguro, H., Watanabe, M., Sato, T., Hikage, F., Furuhashi, M., Okura, M., Hida, T., & Uhara, H. (2023) · Cells · doi:10.3390/cells12050759 · Cited by 20 · see citing works
Pathology and Molecular Biology of Melanoma
Timis, T., Bergþorsson, J. Þ., Greiff, V., Cenariu, M., & Cenariu, D. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45070352 · Cited by 20 · see citing works
Three-dimensional epithelial cultures: a tool to model cancer development and progression.
Eritja, N., Dolcet, X., & Matías‐Guiu, X. (2013) · PubMed · doi:10.14670/hh-28.1245 · Cited by 16 · see citing works
Li, Z., Wang, F., Dang, J., Cheng, F., & Zheng, F. (2022) · Translational Cancer Research · doi:10.21037/tcr-22-292 · Cited by 14 · see citing works
Ranjan, A., & Kalraiya, R. D. (2014) · BioMed Research International · doi:10.1155/2014/804680 · Cited by 13 · see citing works
3D-spheroids: What can they tell us about pancreatic ductal adenocarcinoma cell phenotype?
Gagliano, N., Sforza, C., Sommariva, M., Menon, A., Conte, V., Sartori, P., & Procacci, P. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.05.027 · Cited by 12 · see citing works
Self-citationKielosto, M., Eriksson, J., Nummela, P., Yin, M., & Hölttä, E. (2018) · Oncotarget · doi:10.18632/oncotarget.26508 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Shah, S., & D’Souza, G. G. M. (2025) · Cells · doi:10.3390/cells14100732 · Cited by 66 · see citing works
“In one comparative study, transcriptomic analysis of melanoma cells cultured as monolayers, monolayers with ECM, and spheroids revealed that gene expression remained largely unchanged between the two monolayer conditions, while spheroid cultures exhibited substantial differences [194,195].”
- Authors
- Fontana, F., Sommariva, M., Anselmi, M., Bianchi, F., Limonta, P., & Gagliano, N.
- Affiliations
- University of Milan (IT)
- Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Università degli Studi di Milano, 20133 Milan, Italy
- Corresponding author
- Gagliano, Nicoletta
- ORCID
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2024-01-17
- Volume
- 13
- Issue
- 2
- Pages
- 181
- ISSN
- 2073-4409 (ISSN-L)
- PMC
- PMC10814891
- OpenAlex
- W4390985470
- Cited by
- 11
- References
- 93
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 2
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cells (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Seal of Excellence—SoE SEED 2020, Università degli Studi di Milano
- AIRC fellowship for Italy
- Fondazione Umberto Veronesi
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- melanoma, epithelial-mesenchymal transition, multicellular spheroids, monolayer culture, A375 cells, EMT markers, N-cadherin, E-cadherin, vimentin, cortical actin, ZEB1, Slug, snails, Twist, TGF-β1, lysyl oxidase, cell invasion, metastasis, tumor cell differentiation
- MeSH terms
- Cell Culture Techniques, Three Dimensional, Cell Differentiation, Humans, Melanoma, Phenotype, Epithelial-Mesenchymal Transition
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
