Bioengineered 3D platform to explore cell–ECM interactions and drug resistance of epithelial ovarian cancer cells
Open accessAbstract
The behaviour of cells cultured within three-dimensional (3D) structures rather than onto two-dimensional (2D) culture plastic more closely reflects their in vivo responses. Consequently, 3D culture systems are becoming crucial scientific tools in cancer cell research. We used a novel 3D culture concept to assess cell-matrix interactions implicated in carcinogenesis: a synthetic hydrogel matrix equipped with key biomimetic features, namely incorporated cell integrin-binding motifs (e.g. RGD peptides) and the ability of being degraded by cell-secreted proteases (e.g. matrix metalloproteases). As a cell model, we chose epithelial ovarian cancer, an aggressive disease typically diagnosed at an advanced stage when chemoresistance occurs. Both cell lines used (OV-MZ-6, SKOV-3) proliferated similarly in 2D, but not in 3D. Spheroid formation was observed exclusively in 3D when cells were embedded within hydrogels. By exploiting the design flexibility of the hydrogel characteristics, we showed that proliferation in 3D was dependent on cell-integrin engagement and the ability of cells to proteolytically remodel their extracellular microenvironment. Higher survival rates after exposure to the anti-cancer drug paclitaxel were observed in cell spheroids grown in hydrogels (40-60%) compared to cell monolayers in 2D (20%). Thus, 2D evaluation of chemosensitivity may not reflect pathophysiological events seen in patients. Because of the design flexibility of their characteristics and their stability in long-term cultures (28 days), these biomimetic hydrogels represent alternative culture systems for the increasing demand in cancer research for more versatile, physiologically relevant and reproducible 3D matrices.
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Cells cultured in 3D models are more resistant to anticancer drugs than 2D cultures.
“A number of studies have found that cells cultured in 3D models are more resistant to anticancer drugs than 2D cultures. 41,56”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [41]
Ovarian cancer cell survival and proliferation in 3D cultures after paclitaxel treatment was reduced by 40% or 60% in 3D cell spheroids, while the same treatment led to 80% reduced cell viability in the 2D cell monolayer.
“For example, ovarian cancer cell survival and proliferation in 3D cultures after paclitaxel treatment was reduced by 40% or 60% in 3D cell spheroids, while the same treatment led to 80% reduced cell viability in the 2D cell monolayer. 41”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [41]
2D monolayers might lack critical features associated with in vivo tumor progression, such as hypoxia.
“Additional work has also shown that 2D monolayers might lack critical features associated with in vivo tumor progression, such as hypoxia41,42.”
From Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution (2022) · cites this paper as [41]
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Tissue Cells Feel and Respond to the Stiffness of Their Substrate
Discher, D. E., Janmey, P., & Wang, Y.-L. (2005) · Science · doi:10.1126/science.1116995 · Cited by 6,382 · see citing works
Lutolf, M. P., & Hubbell, J. A. (2005) · Nature Biotechnology · doi:10.1038/nbt1055 · Cited by 4,551 · see citing works
Tensional homeostasis and the malignant phenotype
Paszek, M. J., Zahir, N., Johnson, K. R., Lakins, J. N., Rozenberg, G. I., Gefen, A., Reinhart-King, C. A., Margulies, S. S., Dembo, M., Boettiger, D., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.08.010 · Cited by 3,941 · see citing works
Integrins in cancer: biological implications and therapeutic opportunities
Desgrosellier, J. S., & Cheresh, D. A. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2748 · Cited by 3,721 · see citing works
Designing materials for biology and medicine
Langer, R., & Tirrell, D. A. (2004) · Nature · doi:10.1038/nature02388 · Cited by 3,198 · see citing works
The third dimension bridges the gap between cell culture and live tissue
Pampaloni, F., Reynaud, E. G., & Stelzer, E. H. K. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2236 · Cited by 2,817 · see citing works
Capturing complex 3D tissue physiology in vitro
Griffith, L. G., & Swartz, M. A. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1858 · Cited by 2,274 · see citing works
Bissell, M. J., & Radisky, D. (2001) · Nature Reviews Cancer · doi:10.1038/35094059 · Cited by 2,180 · see citing works
Cell and environment interactions in tumor microregions: the multicell spheroid model.
Sutherland, R. M. (1988) · Science · doi:10.1126/science.2451290 · Cited by 1,803 · see citing works
Modeling Tissue Morphogenesis and Cancer in 3D
Yamada, K. M., & Cukierman, E. (2007) · Cell · doi:10.1016/j.cell.2007.08.006 · Cited by 1,751 · see citing works
Matrigel: Basement membrane matrix with biological activity
Kleinman, H. K., & Martin, G. R. (2005) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2005.05.004 · Cited by 1,673 · see citing works
One Hundred and Twenty-Seven Cultured Human Tumor Cell Lines Producing Tumors in Nude Mice23
Fogh, J., Fogh, J. M., & Orfeo, T. (1977) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/59.1.221 · Cited by 1,599 · see citing works
Lutolf, M. P., Lauer-Fields, J. L., Schmoekel, H. G., Metters, A. T., Weber, F. E., Fields, G. B., & Hubbell, J. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0737381100 · Cited by 1,508 · see citing works
Self-citationWeaver, V. M., Petersen, O. W., Wang, F., Larabell, C. A., Briand, P., Damsky, C., & Bissell, M. J. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.1.231 · Cited by 1,483 · see citing works
Three-dimensional culture models of normal and malignant breast epithelial cells
Lee, G. Y., Kenny, P. A., Lee, E. H., & Bissell, M. J. (2007) · Nature Methods · doi:10.1038/nmeth1015 · Cited by 1,336 · see citing works
Hildebrand, T., Laib, A., Müller, R., Dequeker, J., & Ruegsegger, P. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.7.1167 · Cited by 1,303 · see citing works
Abbott, A. (2003) · Nature · doi:10.1038/424870a · Cited by 1,237 · see citing works
Kleinman, H. K., McGarvey, M. L., Liotta, L. A., Robey, P. G., Tryggvason, K., & Martin, G. R. (1982) · Biochemistry · doi:10.1021/bi00267a025 · Cited by 1,231 · see citing works
Ovarian cancer: strategies for overcoming resistance to chemotherapy
Agarwal, R., & Kaye, S. B. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1123 · Cited by 1,155 · see citing works
Three-Dimensional Cell Culture Matrices: State of the Art
Lee, J., Cuddihy, M. J., & Kotov, N. A. (2008) · Tissue Engineering Part B: Reviews · doi:10.1089/teb.2007.0150 · Cited by 1,047 · see citing works
Modelling glandular epithelial cancers in three-dimensional cultures
Debnath, J., & Brugge, J. S. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1695 · Cited by 1,014 · see citing works
Cell interactions with three-dimensional matrices
Cukierman, E., Pankov, R. G., & Yamada, K. M. (2002) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(02)00364-2 · Cited by 889 · see citing works
Solid stress inhibits the growth of multicellular tumor spheroids
Helmlinger, G., Netti, P. A., Lichtenbeld, H. C., Melder, R. J., & Jain, R. K. (1997) · Nature Biotechnology · doi:10.1038/nbt0897-778 · Cited by 859 · see citing works
Repair of bone defects using synthetic mimetics of collagenous extracellular matrices
Lutolf, M. P., Weber, F. E., Schmoekel, H. G., Schense, J. C., Kohler, T., Müller, R., & Hubbell, J. A. (2003) · Nature Biotechnology · doi:10.1038/nbt818 · Cited by 850 · see citing works
Self-citationWeaver, V. M., Lelièvre, S. A., Lakins, J. N., Chrenek, M. A., Jones, J., Giancotti, F. G., Werb, Z., & Bissell, M. J. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00125-3 · Cited by 794 · see citing works
Modeling tissue-specific signaling and organ function in three dimensions
Schmeichel, K. L., & Bissell, M. J. (2003) · Journal of Cell Science · doi:10.1242/jcs.00503 · Cited by 583 · see citing works
Raeber, G. P., Lütolf, M. P., & Hubbell, J. A. (2005) · Biophysical Journal · doi:10.1529/biophysj.104.050682 · Cited by 576 · see citing works
Cushing, M. C., & Anseth, K. S. (2007) · Science · doi:10.1126/science.1140171 · Cited by 520 · see citing works
Multicellular spheroids in ovarian cancer metastases: Biology and pathology
Shield, K., Ackland, M. L., Ahmed, N., & Rice, G. E. (2009) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.11.032 · Cited by 412 · see citing works
Kenny, H. A., Kaur, S., Coussens, L. M., & Lengyel, E. R. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33775 · Cited by 370 · see citing works
Weigelt, B., Lo, A. T., Park, C. C., Gray, J. W., & Bissell, M. J. (2009) · Breast Cancer Research and Treatment · doi:10.1007/s10549-009-0502-2 · Cited by 336 · see citing works
The effect of matrix characteristics on fibroblast proliferation in 3D gels
Bott, K., Upton, Z., Schrobback, K., Ehrbar, M., Hubbell, J. A., Lütolf, M. P., & Rizzi, S. C. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.07.046 · Cited by 328 · see citing works
Self-citationMulticellular spheroids: a three‐dimensionalin vitroculture system to study tumour biology
Kunz‐Schughart, L. A., Kreutz, M. P., & Knuechel, R. (1998) · International Journal of Experimental Pathology · doi:10.1046/j.1365-2613.1998.00051.x · Cited by 326 · see citing works
Biomaterials offer cancer research the third dimension
Hutmacher, D. W. (2010) · Nature Materials · doi:10.1038/nmat2619 · Cited by 324 · see citing works
Self-citationCancer cell angiogenic capability is regulated by 3D culture and integrin engagement
Fischbach, C., Kong, H. J., Hsiong, S. X., Evangelista, M. B., Yuen, W. W., & Mooney, D. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808932106 · Cited by 312 · see citing works
Biomolecular Hydrogels Formed and Degraded via Site-Specific Enzymatic Reactions
Ehrbar, M., Rizzi, S. C., Schoenmakers, R. G., Miguel, B. S., Hubbell, J. A., Weber, F. E., & Lütolf, M. P. (2007) · Biomacromolecules · doi:10.1021/bm070228f · Cited by 299 · see citing works
Self-citationFocus on epithelial ovarian cancer
Ozols, R. F., Bookman, M. A., Connolly, D. C., Daly, M. B., Godwin, A. K., Schilder, R. J., Xu, X., & Hamilton, T. C. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00002-9 · Cited by 291 · see citing works
Unraveling the microenvironmental influences on the normal mammary gland and breast cancer
Weigelt, B., & Bissell, M. J. (2008) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2008.03.013 · Cited by 274 · see citing works
Sodek, K. L., Ringuette, M. J., & Brown, T. J. (2009) · International Journal of Cancer · doi:10.1002/ijc.24188 · Cited by 248 · see citing works
Kenny, H. A., Krausz, T., Yamada, S. D., & Lengyel, E. (2007) · International Journal of Cancer · doi:10.1002/ijc.22874 · Cited by 243 · see citing works
Can tissue engineering concepts advance tumor biology research?
Hutmacher, D. W., Loessner, D., Rizzi, S. C., Kaplan, D. L., Mooney, D. J., & Clements, J. A. (2010) · Trends in biotechnology · doi:10.1016/j.tibtech.2009.12.001 · Cited by 237 · see citing works
Self-citationEnzymatic formation of modular cell-instructive fibrin analogs for tissue engineering
Ehrbar, M., Rizzi, S. C., Hlushchuk, R., Djonov, V., Zisch, A. H., Hubbell, J. A., Weber, F. E., & Lütolf, M. P. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.03.027 · Cited by 232 · see citing works
Self-citationLütolf, M. P. (2009) · Nature Materials · doi:10.1038/nmat2458 · Cited by 230 · see citing works
CD44 and β1 Integrin Mediate Ovarian Carcinoma Cell Adhesion to Peritoneal Mesothelial Cells
Lessan, K., Aguiar, D. J., Oegema, T. R., Siebenson, L., & Skubitz, A. P. N. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65406-5 · Cited by 226 · see citing works
β1-Integrins Regulate the Formation and Adhesion of Ovarian Carcinoma Multicellular Spheroids
Casey, R. C., Burleson, K. M., Skubitz, K. M., Pambuccian, S. E., Oegema, T. R., Ruff, L. E., & Skubitz, A. P. N. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63058-1 · Cited by 225 · see citing works
Quent, V. M. C., Loessner, D., Friis, T., Reichert, J. C., & Hutmacher, D. W. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01013.x · Cited by 215 · see citing works
Self-citationMolecular description of a 3D in vitro model for the study of epithelial ovarian cancer (EOC)
Zietarska, M., Maugard, C. M., Filali‐Mouhim, A., Alam‐Fahmy, M., Tonin, P. N., Provencher, D. M., & Mes‐Masson, A. (2007) · Molecular Carcinogenesis · doi:10.1002/mc.20315 · Cited by 209 · see citing works
Rizzi, S. C., Ehrbar, M., Halstenberg, S., Raeber, G. P., Schmoekel, H. G., Hagenmüller, H., Müller, R., Weber, F. E., & Hubbell, J. A. (2006) · Biomacromolecules · doi:10.1021/bm060504a · Cited by 193 · see citing works
Self-citationHudson, L. G., Zeineldin, R., & Stack, M. S. (2008) · Clinical & Experimental Metastasis · doi:10.1007/s10585-008-9171-5 · Cited by 186 · see citing works
Serebriiskii, I. G., Castelló-Cros, R., Lamb, A., Golemis, E. A., & Cukierman, E. (2008) · Matrix Biology · doi:10.1016/j.matbio.2008.02.008 · Cited by 176 · see citing works
Prestwich, G. D. (2007) · Accounts of Chemical Research · doi:10.1021/ar7000827 · Cited by 176 · see citing works
Frankel, A., Buckman, R. A., & Kerbel, R. S. (1997) · PubMed · Cited by 168 · see citing works
Guilak, F. (1994) · Journal of Microscopy · doi:10.1111/j.1365-2818.1994.tb03447.x · Cited by 149 · see citing works
Burleson, K. M., Hansen, L. K., & Skubitz, A. P. N. (2005) · Clinical & Experimental Metastasis · doi:10.1007/s10585-004-5768-5 · Cited by 144 · see citing works
Translating tissue engineering technology platforms into cancer research
Hutmacher, D. W., Horch, R. E., Loessner, D., Rizzi, S. C., Sieh, S., Reichert, J. C., Clements, J. A., Beier, J. P., Arkudas, A., Bleiziffer, O., et al. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00853.x · Cited by 136 · see citing works
Self-citationLee, S. T., Yun, J. I., Jo, Y. S., Mochizuki, M., van der Vlies, A. J., Kontos, S., Ihm, J. E., Lim, J. M., & Hubbell, J. A. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.10.054 · Cited by 134 · see citing works
Modeling Morphogenesis and Oncogenesis in Three-Dimensional Breast Epithelial Cultures
Hebner, C. M., Weaver, V. M., & Debnath, J. (2008) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.3.121806.151526 · Cited by 122 · see citing works
Shield, K., Riley, C. B., Quinn, M. A., Rice, G. E., Ackland, M. L., & Ahmed, N. (2007) · Journal of Carcinogenesis · doi:10.1186/1477-3163-6-11 · Cited by 119 · see citing works
Moss, N. M., Barbolina, M. V., Liu, Y., Sun, L., Munshi, H. G., & Stack, M. S. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4151 · Cited by 105 · see citing works
Kenny, H. A., Dogan, S., Zillhardt, M., Mitra, A. K., Yamada, S. D., Krausz, T. N., & Lengyel, E. R. (2009) · Cancer treatment and research · doi:10.1007/978-0-387-98094-2_16 · Cited by 91 · see citing works
Dong, Y., Tan, O. L., Loessner, D., Stephens, C. R., Walpole, C., Boyle, G. M., Parsons, P. G., & Clements, J. A. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-3415 · Cited by 91 · see citing works
Self-citationFactors affecting growth and drug sensitivity of mouse mammary tumor lines in collagen gel cultures.
Miller, B. E., Miller, F. R., & Heppner, G. H. (1985) · PubMed · Cited by 88 · see citing works
Möbus, V. J., Gerharz, C. D., Press, U., et al. (1992) · International Journal of Cancer · doi:10.1002/ijc.2910520115 · Cited by 87 · see citing works
Integration column: Artificial ECM: expanding the cell biology toolbox in 3D
Lütolf, M. P. (2009) · Integrative Biology · doi:10.1039/b902243k · Cited by 81 · see citing works
Taxol-induced bcl-2 phosphorylation in ovarian cancer cell monolayer and spheroids.
Makhija, S. K., Taylor, D. D., Gibb, R. K., & Gerçel-Taylor, Ç. (1999) · International Journal of Oncology · doi:10.3892/ijo.14.3.515 · Cited by 51 · see citing works
Human Ovarian Adenocarcinoma Cells Synthesize Vitronectin and Use It to Organize Their Adhesion
Carreiras, F., Cruet, S., Staedel, C., et al. (1999) · Gynecologic Oncology · doi:10.1006/gyno.1998.5262 · Cited by 50 · see citing works
Imaging and quantifying the dynamics of tumor-associated proteolysis
Sameni, M., Cavallo‐Medved, D., Dosescu, J., Jedeszko, C., Moin, K., Mullins, S., Olive, M. B., Rudy, D., & Sloane, B. F. (2008) · Clinical & Experimental Metastasis · doi:10.1007/s10585-008-9218-7 · Cited by 50 · see citing works
Modelling molecular mechanisms of breast cancer and invasion: lessons from the normal gland
Bissell, M. J. (2007) · Biochemical Society Transactions · doi:10.1042/bst0350018 · Cited by 41 · see citing works
Sowa, M. B., Chrisler, W., Zens, K. D., Ashjian, E. J., & Opresko, L. K. (2010) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2010.03.004 · Cited by 32 · see citing works
Loessner, D., Abou‐Ajram, C., Benge, A., et al. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.05.014 · Cited by 30 · see citing works
Self-citationLoessner, D., Kessler, H., Thumshirn, G., et al. (2006) · Analytical Chemistry · doi:10.1021/ac052078+ · Cited by 21 · see citing works
Self-citationStok, K. S., & Müller, R. (2009) · Microscopy Research and Technique · doi:10.1002/jemt.20713 · Cited by 18 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Edmondson, R., Broglie, J. J., Adcock, A. F., & Yang, L. (2014) · ASSAY and Drug Development Technologies · doi:10.1089/adt.2014.573 · Cited by 2,515 · see citing works
Loessner, D., Meinert, C., Kaemmerer, E., Martine, L. C., Yue, K., Levett, P. A., Klein, T. J., Melchels, F. P. W., Khademhosseini, A., & Hutmacher, D. W. (2016) · Nature Protocols · doi:10.1038/nprot.2016.037 · Cited by 868 · see citing works
Self-citationHoarau-Véchot, J., Rafii, A., Touboul, C., & Pasquier, J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010181 · Cited by 489 · see citing works
Challenges of applying multicellular tumor spheroids in preclinical phase
Han, S. J., Kwon, S., & Kim, K. S. (2021) · Cancer Cell International · doi:10.1186/s12935-021-01853-8 · Cited by 428 · see citing works
Bioprinting for cancer research
Knowlton, S., Onal, S., Yu, C. H., Zhao, J. J., & Tasoglu, S. (2015) · Trends in Biotechnology · doi:10.1016/j.tibtech.2015.06.007 · Cited by 361 · see citing works
CRISPR screens in cancer spheroids identify 3D growth-specific vulnerabilities
Han, K., Pierce, S. E., Li, A., Spees, K., Anderson, G. R., Seoane, J. A., Lo, Y.-H., Dubreuil, M., Olivas, M., Kamber, R. A., et al. (2020) · Nature · doi:10.1038/s41586-020-2099-x · Cited by 311 · see citing works
Stock, K., Estrada, M. F., Vidic, S., Gjerde, K., Rudisch, A., Santo, V. E., Barbier, M., Blom, S., Arundkar, S. C., Selvam, I., et al. (2016) · Scientific Reports · doi:10.1038/srep28951 · Cited by 253 · see citing works
Comparative stability studies of poly(2-methyl-2-oxazoline) and poly(ethylene glycol) brush coatings
Pidhatika, B., Rodenstein, M., Chen, Y., Rakhmatullina, E., Mühlebach, A., Acikgöz, C., Textor, M., & Konradi, R. (2012) · Biointerphases · doi:10.1007/s13758-011-0001-y · Cited by 251 · see citing works
Gelatine Methacrylamide-Based Hydrogels: An Alternative Three-Dimensional Cancer Cell Culture System
Kaemmerer, E., Melchels, F. P. W., Holzapfel, B. M., Meckel, T., Hutmacher, D. W., & Loessner, D. (2014) · Acta Biomaterialia · doi:10.1016/j.actbio.2014.02.035 · Cited by 219 · see citing works
Self-citationDrug discovery through stem cell-based organoid models
Ranga, A., Gjorevski, N., & Lutolf, M. P. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.02.006 · Cited by 195 · see citing works
Fey, S. J., & Wrzesinski, K. (2012) · Toxicological Sciences · doi:10.1093/toxsci/kfs122 · Cited by 188 · see citing works
Microfluidic 3D models of cancer
Sung, K. E., & Beebe, D. J. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.07.002 · Cited by 190 · see citing works
Hongisto, V., Jernström, S., Fey, V., Mpindi, J.-P., Kleivi Sahlberg, K., Kallioniemi, O., & Perälä, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077232 · Cited by 181 · see citing works
Simulation of complex transport of nanoparticles around a tumor using tumor-microenvironment-on-chip
Kwak, B., Ozcelikkale, A., Shin, C. S., Park, K., & Han, B. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.08.027 · Cited by 165 · see citing works
Candiello, J., Grandhi, T. S. P., Goh, S. K., Vaidya, V., Lemmon-Kishi, M., Eliato, K. R., Ros, R., Kumta, P. N., Rege, K., & Banerjee, I. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.05.031 · Cited by 146 · see citing works
Bioengineered 3D models of human pancreatic cancer recapitulate in vivo tumour biology
Osuna de la Peña, D., Trabulo, S. M. D., Collin, E., Liu, Y., Sharma, S., Tatari, M., Behrens, D., Erkan, M., Lawlor, R. T., Scarpa, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25921-9 · Cited by 138 · see citing works
Self-citationBreast Cancer Cell Invasion into a Three Dimensional Tumor-Stroma Microenvironment
Truong, D., Puleo, J., Llave, A., Mouneimne, G., Kamm, R. D., & Nikkhah, M. (2016) · Scientific Reports · doi:10.1038/srep34094 · Cited by 135 · see citing works
Biomimetic Model of Tumor Microenvironment on Microfluidic Platform
Chung, M., Ahn, J., Son, K., Kim, S., & Jeon, N. L. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700196 · Cited by 126 · see citing works
Li, W., Zhou, Z., Zhou, X., Khoo, B. L., Gunawan, R., Chin, Y. R., Zhang, L., Yi, C., Guan, X., & Yang, M. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202202609 · Cited by 109 · 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
Toward the broad adoption of 3D tumor models in the cancer drug pipeline
Cox, M. C., Reese, L. M., Bickford, L. R., & Verbridge, S. S. (2015) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.5b00172 · Cited by 80 · see citing works
Mieulet, V., Garnier, C., Kieffer, Y., Guilbert, T., Nemati, F., Marangoni, E., Renault, G., Chamming’s, F., Vincent-Salomon, A., & Mechta-Grigoriou, F. (2021) · Scientific Reports · doi:10.1038/s41598-021-83685-0 · Cited by 79 · see citing works
Peptide-protein Coassembling Matrices as a Biomimetic 3D Model of Ovarian Cancer
Hedegaard, C. L., Redondo-Gómez, C., Tan, B. Y., Ng, K. W., Loessner, D., & Mata, A. (2020) · Science Advances · doi:10.1126/sciadv.abb3298 · Cited by 76 · see citing works
Ekert, J. E., Deakyne, J., Pribul-Allen, P., Terry, R., Schofield, C., Jeong, C. G., Storey, J., Mohamet, L., Francis, J., Naidoo, A., et al. (2020) · SLAS DISCOVERY · doi:10.1177/2472555220923332 · Cited by 68 · see citing works
Drifka, C. R., Eliceiri, K. W., Weber, S. M., & Kao, W. J. (2013) · Lab on a Chip · doi:10.1039/c3lc50487e · Cited by 64 · see citing works
An omentum-inspired 3d peg hydrogel for identifying ecm-drivers of drug resistant ovarian cancer
Brooks, E. A., Gencoglu, M. F., Corbett, D. C., Stevens, K. R., & Peyton, S. R. (2019) · APL Bioengineering · doi:10.1063/1.5091713 · Cited by 51 · see citing works
Han, B., Qu, C., Park, K., Konieczny, S. F., & Korc, M. (2016) · Cancer Letters · doi:10.1016/j.canlet.2015.12.003 · Cited by 53 · see citing works
Progress 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
Blache, U., Horton, E. R., Xia, T., Schoof, E. M., Blicher, L. H., Schönenberger, A., Snedeker, J. G., Martin, I., Erler, J. T., & Ehrbar, M. (2019) · Life Science Alliance · doi:10.26508/lsa.201900304 · Cited by 49 · see citing works
A biomimetic tumor model of heterogeneous invasion in pancreatic ductal adenocarcinoma
Bradney, M. J., Venis, S. M., Yang, Y., Konieczny, S. F., & Han, B. (2020) · Small · doi:10.1002/smll.201905500 · Cited by 38 · see citing works
3D fluid-dynamic ovarian cancer model resembling systemic drug administration for efficacy assay
Marrella, A. (2020) · ALTEX · doi:10.14573/altex.2003131 · Cited by 36 · see citing works
Xia, Y., Chen, H., Li, J., Hu, H., Qian, Q., He, R.-X., Ding, Z., & Guo, S.-S. (2021) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.1c06655 · Cited by 35 · see citing works
3D Tumor Spheroid Models for In Vitro Therapeutic Screening of Nanoparticles
Daunys, S., Janonienė, A., Januškevičienė, I., Paškevičiūtė, M., & Petrikaitė, V. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-58174-9_11 · Cited by 32 · see citing works
Heredia-Soto, V., Redondo, A., Berjón, A., Miguel-Martín, M., Díaz, E., Crespo, R., Hernández, A., Yébenes, L., Gallego, A., Feliu, J., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.25098 · Cited by 33 · see citing works
Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution
Monberg, M. E., Geiger, H., Lee, J. J., Sharma, R., Semaan, A., Bernard, V., Wong, J., Wang, F., Liang, S., Swartzlander, D. B., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31376-3 · Cited by 30 · see citing works
Zuchowska, A., Marciniak, K., Bazylinska, U., Jastrzebska, E., Wilk, K. A., & Brzozka, Z. (2018) · Sensors and Actuators B: Chemical · doi:10.1016/j.snb.2018.08.037 · Cited by 22 · see citing works
The many microenvironments of ovarian cancer
Micek, H. M., Visetsouk, M. R., Fleszar, A. J., & Kreeger, P. K. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-59038-3_12 · Cited by 14 · see citing works
Fabrication of micro-cages and caged tumor spheroids for microfluidic chip-based assays
He, Y., Huang, B., Rofaani, E., Hu, J., Liu, Y., Pitingolo, G., Wang, L., Shi, J., Aimé, C., & Chen, Y. (2020) · Microelectronic Engineering · doi:10.1016/j.mee.2020.111256 · Cited by 13 · see citing works
Generation of a Three-Dimensional In Vitro Ovarian Cancer Co-culture Model for Drug Screening Assays
Tofani, L. B., Sousa, L. O., Luiz, M. T., Abriata, J. P., Marchetti, J. M., Leopoldino, A. M., & Swiech, K. (2021) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2021.04.003 · Cited by 14 · see citing works
- Authors
- Loessner, D., Stok, K. S., Lutolf, M. P., Hutmacher, D. W., Clements, J. A., & Rizzi, S. C.
- Affiliations
- Queensland University of Technology (AU)
- ETH Zurich (CH)
- Corresponding author
- Clements, Judith A.
- Rizzi, Simone C.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2010-11
- Volume
- 31
- Issue
- 32
- Pages
- 8494-8506
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2123232388
- Cited by
- 602
- References
- 72
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 22 · 2023: 36 · 2022: 54 · 2021: 59 · 2020: 68 · 2019: 35 · 2018: 39 · 2017: 56 · 2016: 49 · 2015: 36 · 2014: 51 · 2013: 41 · 2012: 21
- FWCI
- 10.28
- Type
- journal article
- Language
- en
- Open access
- green
- purl.org
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- QUT ePrints (Queensland University of Technology) (submittedVersion, cc-by-nc-nd)
- Figshare (submittedVersion, cc-by)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Queensland University of Technology
- Queensland Government
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- 3D cell culture, biomimetic hydrogels, cell-matrix interactions, epithelial ovarian cancer, chemoresistance, paclitaxel, cell spheroids, integrin binding, RGD peptide, matrix metalloproteinases, extracellular matrix remodeling, SKOV3, tumor cell proliferation
- MeSH terms
- Antineoplastic Agents, Phytogenic, Cell Survival, Epithelial Cells, Female, Humans, Oligopeptides, Ovarian Neoplasms, Polyethylene Glycols, Integrins, Paclitaxel, Spheroids, Cellular, Drug Resistance, Neoplasm, Hydrogel, Polyethylene Glycol Dimethacrylate, Biomimetic Materials, Cell Line, Tumor, Mechanical Phenomena, Bioengineering
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