REVIEW
Review on biofabrication and applications of heterogeneous tumor models
Tiankun Liu,
Rui Yao,
Yuan Pang,
Wei Sun,
Tiankun Liu
Tsinghua University, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, People's Republic of China
Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Tsinghua University, 111 “Biomanufacturing and Engineering Living Systems” Innovation International Talents Base, Beijing, People's Republic of China
Key Laboratory of Advanced Forming and Manufacturing, Ministry of Education, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Search for more papers by this authorRui Yao
Tsinghua University, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, People's Republic of China
Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Tsinghua University, 111 “Biomanufacturing and Engineering Living Systems” Innovation International Talents Base, Beijing, People's Republic of China
Key Laboratory of Advanced Forming and Manufacturing, Ministry of Education, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Search for more papers by this authorYuan Pang
Tsinghua University, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, People's Republic of China
Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Tsinghua University, 111 “Biomanufacturing and Engineering Living Systems” Innovation International Talents Base, Beijing, People's Republic of China
Key Laboratory of Advanced Forming and Manufacturing, Ministry of Education, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Search for more papers by this authorCorresponding Author
Wei Sun
Tsinghua University, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, People's Republic of China
Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Tsinghua University, 111 “Biomanufacturing and Engineering Living Systems” Innovation International Talents Base, Beijing, People's Republic of China
Key Laboratory of Advanced Forming and Manufacturing, Ministry of Education, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Department of Mechanical Engineering, Drexel University, Philadelphia, PA
Correspondence
Wei Sun, Department of Mechanical Engineering, Tsinghua University, Room A743, Lee Shau Kee Science and Technology Building, Haidian District, Beijing 100084, China.
Email: [email protected]
Search for more papers by this authorTiankun Liu,
Rui Yao,
Yuan Pang,
Wei Sun,
Tiankun Liu
Tsinghua University, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, People's Republic of China
Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Tsinghua University, 111 “Biomanufacturing and Engineering Living Systems” Innovation International Talents Base, Beijing, People's Republic of China
Key Laboratory of Advanced Forming and Manufacturing, Ministry of Education, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Search for more papers by this authorRui Yao
Tsinghua University, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, People's Republic of China
Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Tsinghua University, 111 “Biomanufacturing and Engineering Living Systems” Innovation International Talents Base, Beijing, People's Republic of China
Key Laboratory of Advanced Forming and Manufacturing, Ministry of Education, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Search for more papers by this authorYuan Pang
Tsinghua University, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, People's Republic of China
Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Tsinghua University, 111 “Biomanufacturing and Engineering Living Systems” Innovation International Talents Base, Beijing, People's Republic of China
Key Laboratory of Advanced Forming and Manufacturing, Ministry of Education, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Search for more papers by this authorCorresponding Author
Wei Sun
Tsinghua University, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, People's Republic of China
Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Tsinghua University, 111 “Biomanufacturing and Engineering Living Systems” Innovation International Talents Base, Beijing, People's Republic of China
Key Laboratory of Advanced Forming and Manufacturing, Ministry of Education, Department of Mechanical Engineering, Tsinghua University, Beijing, People's Republic of China
Department of Mechanical Engineering, Drexel University, Philadelphia, PA
Correspondence
Wei Sun, Department of Mechanical Engineering, Tsinghua University, Room A743, Lee Shau Kee Science and Technology Building, Haidian District, Beijing 100084, China.
Email: [email protected]
Search for more papers by this authorAbstract
Resolving the origin and development of tumor heterogeneity has proven to be a crucial challenge in cancer research. In vitro tumor models have been widely used for both scientific and clinical research. Currently, tumor models based on 2D cell culture, animal models, and 3D cell-laden constructs are widely used. Heterogeneous tumor models, which consist of more than one cell type and mimic cell–cell as well as cell–matrix interactions, are attracting increasing attention. Heterogeneous tumor models can serve as pathological models to study the microenvironment and tumor development such as tumorigenesis, invasiveness, and malignancy. They also provide disease models for drug screening and personalized therapy. In this review, the current techniques, models, and oncological applications regarding 3D heterogeneous tumor models are summarized and discussed.
CONFLICT OF INTEREST
The authors have declared that there is no conflict of interest.
REFERENCES
- Afrimzon, E., Botchkina, G., Zurgil, N., Shafran, Y., Sobolev, M., Moshkov, S., … Deutsch, M. (2016). Hydrogel microstructure live-cell array for multiplexed analyses of cancer stem cells, tumor heterogeneity and differential drug response at single-element resolution. Lab on a Chip, 16(6), 1047–1062. https://doi.org/10.1039/C6LC00014B
- Alarcón, T., Byrne, H. M., & Maini, P. K. (2003). A cellular automaton model for tumour growth in inhomogeneous environment. Journal of Theoretical Biology, 225(2), 257–274. https://doi.org/10.1016/S0022-5193(03)00244-3
- Albritton, J. L., & Miller, J. S. (2017). 3D bioprinting: Improving in vitro models of metastasis with heterogeneous tumor microenvironments. Disease Models & Mechanisms, 10(1), 3–14. https://doi.org/10.1242/dmm.025049
- Angeloni, V., Contessi, N., De Marco, C., Bertoldi, S., Tanzi, M. C., Daidone, M. G., & Fare, S. (2017). Polyurethane foam scaffold as in vitro model for breast cancer bone metastasis. Acta Biomaterialia, 63, 306–316. https://doi.org/10.1016/j.actbio.2017.09.017
- Araujo, R. P., & McElwain, D. (2004). A history of the study of solid tumour growth: The contribution of mathematical modelling. Bulletin of Mathematical Biology, 66(5), 1039–1091. https://doi.org/10.1016/j.bulm.2003.11.002
- Au, A. K., Huynh, W., Horowitz, L. F., & Folch, A. (2016). 3D-printed microfluidics. Angewandte Chemie International Edition, 55(12), 3862–3881. https://doi.org/10.1002/anie.201504382
- Bachmann, J., Raue, A., Schilling, M., Becker, V., Timmer, J., & Klingmueller, U. (2012). Predictive mathematical models of cancer signalling pathways. Journal of Internal Medicine, 271(2), 155–165. https://doi.org/10.1111/j.1365-2796.2011.02492.x
- Barbolosi, D., Ciccolini, J., Lacarelle, B., Barlési, F., & André, N. (2015). Computational oncology — mathematical modelling of drug regimens for precision medicine. Nature Reviews Clinical Oncology, 13(4), 242–254. https://doi.org/10.1038/nrclinonc.2015.204
- Becker, J. C., Andersen, M. H., Schrama, D., & Straten, P. T. (2013). Immune-suppressive properties of the tumor microenvironment. Cancer Immunology Immunotherapy, 62(7), 1137–1148. https://doi.org/10.1007/s00262-013-1434-6
- Bedard, P. L., Hansen, A. R., Ratain, M. J., & Siu, L. L. (2013). Tumour heterogeneity in the clinic. Nature, 501(7467), 355–364. https://doi.org/10.1038/nature12627
- Beerenwinkel, N., Schwarz, R. F., Gerstung, M., & Markowetz, F. (2014). Cancer evolution: Mathematical models and computational inference. Systematic Biology, 64(1), e1–e25. https://doi.org/10.1093/sysbio/syu081
- Buchanan, C. F., Voigt, E. E., Szot, C. S., Freeman, J. W., Vlachos, P. P., & Rylander, M. N. (2014). Three-dimensional microfluidic collagen hydrogels for investigating flow-mediated tumor-endothelial signaling and vascular organization. Tissue Engineering Part C—Methods, 20(1), 64–75. https://doi.org/10.1089/ten.tec.2012.0731
- Burrell, R. A., McGranahan, N., Bartek, J., & Swanton, C. (2013). The causes and consequences of genetic heterogeneity in cancer evolution. Nature, 501(7467), 338–345. https://doi.org/10.1038/nature12625
- Cai, Y., Wu, J., Xu, S., & Li, Z. (2013). A hybrid cellular automata model of multicellular tumour spheroid growth in hypoxic microenvironment. Journal of Applied Mathematics (519895), XXX, 1–10. https://doi.org/10.1155/2013/519895
- Carey, S. P., Starchenko, A., McGregor, A. L., & Reinhart-King, C. A. (2013). Leading malignant cells initiate collective epithelial cell invasion in a three-dimensional heterotypic tumor spheroid model. Clinical & Experimental Metastasis, 30(5), 615–630. https://doi.org/10.1007/s10585-013-9565-x
- Carvalho, M. R., Lima, D., Reis, R. L., Correlo, V. M., & Oliveira, J. M. (2015). Evaluating biomaterial- and microfluidic-based 3D tumor models. Trends in Biotechnology, 33(11), 667–678. https://doi.org/10.1016/j.tibtech.2015.09.009
- Casey, J., Yue, X., Nguyen, T. D., Acun, A., Zellmer, V. R., Zhang, S., & Zorlutuna, P. (2017). 3D hydrogel-based microwell arrays as a tumor microenvironment model to study breast cancer growth. Biomed Mater, 12(2), 25009. https://doi.org/10.1088/1748-605X/aa5d5c
- Chen, Y., Zhang, Z., Fouladdel, S., Deol, Y., Ingram, P. N., McDermott, S. P., … Yoon, E. (2016). Single cell dual adherent-suspension co-culture micro-environment for studying tumor-stromal interactions with functionally selected cancer stem-like cells. Lab on a Chip, 16(15), 2935–2945. https://doi.org/10.1039/C6LC00062B
- Christakou, A. E., Ohlin, M., Onfelt, B., & Wiklund, M. (2015). Ultrasonic three-dimensional on-chip cell culture for dynamic studies of tumor immune surveillance by natural killer cells. Lab Chip, 15(15), 3222–3231. https://doi.org/10.1039/c5lc00436e
- Curtis, C., Shah, S. P., Chin, S., Turashvili, G., Rueda, O. M., Dunning, M. J., … Aparicio, S. (2012). The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature, 486(7403), 346–352. https://doi.org/10.1038/nature10983
- Dababneh, A. B., & Ozbolat, I. T. (2014). Bioprinting technology: A current state-of-the-art review. Journal of Manufacturing Science and Engineering—Transactions of the ASME, 136(0610166SI), 136, 061016. https://doi.org/10.1115/1.4028512
- Dai, X., Liu, L., Ouyang, J., Li, X., Zhang, X., Lan, Q., & Xu, T. (2017). Coaxial 3D bioprinting of self-assembled multicellular heterogeneous tumor fibers. Scientific Reports, 7(1), 1457.
- DelNero, P., Song, Y. H., & Fischbach, C. (2013). Microengineered tumor models: Insights & opportunities from a physical sciences–oncology perspective. Biomedical Microdevices, 15(4), 583–593. https://doi.org/10.1007/s10544-013-9763-y
- de Pillis, L., Fister, K. R., Gu, W., Collins, C., Daub, M., Gross, D., … Preskill, B. (2009). Mathematical model creation for cancer chemo-immunotherapy. Computational and Mathematical Methods in Medicine, 10(PII 9085830233), 165–184.
- Dhurjati, R., Krishnan, V., Shuman, L. A., Mastro, A. M., & Vogler, E. A. (2008). Metastatic breast cancer cells colonize and degrade three-dimensional osteoblastic tissue in vitro. Clinical & experimental metastasis, 25(7), 741.
- Domcke, S., Sinha, R., Levine, D. A., Sander, C., & Schultz, N. (2013). Evaluating cell lines as tumour models by comparison of genomic profiles. Nature Communications, 4(2126). https://doi.org/10.1038/ncomms3126
- Dutta, R. C., & Dutta, A. K. (2009). Cell-interactive 3D-scaffold; advances and applications. Biotechnology Advances, 27(4), 334–339. https://doi.org/10.1016/j.biotechadv.2009.02.002
- Ehsan, S. M., Welch-Reardon, K. M., Waterman, M. L., Hughes, C. C. W., & George, S. C. (2014). A three-dimensional in vitro model of tumor cell intravasation. Integrative Biology, 6(6), 603–610. https://doi.org/10.1039/c3ib40170g
- Estrada, M. F., Rebelo, S. P., Davies, E. J., Pinto, M. T., Pereira, H., Santo, V. E., … Brito, C. (2016). Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression. Biomaterials, 78, 50–61. https://doi.org/10.1016/j.biomaterials.2015.11.030
- Estrella, V., Chen, T., Lloyd, M., Wojtkowiak, J., Cornnell, H. H., Ibrahim-Hashim, A., … Gillies, R. J. (2013). Acidity generated by the tumor microenvironment drives local invasion. Cancer Research, 73(5), 1524–1535. https://doi.org/10.1158/0008-5472.CAN-12-2796
- Fang, X., Sittadjody, S., Gyabaah, K., Opara, E. C., & Balaji, K. C. (2013). Novel 3D co-culture model for epithelial-stromal cells interaction in prostate cancer. PLoS ONE, 8(UNSP e751879). https://doi.org/10.1371/journal.pone.0075187
- Fidler, I. J. (1986). Rationale and methods for the use of nude mice to study the biology and therapy of human cancer metastasis. Cancer Metastasis Rev, 5(1), 29–49. https://doi.org/10.1007/BF00049529
- Fong, E. L. S., Wan, X., Yang, J., Morgado, M., Mikos, A. G., Harrington, D. A., … Farach-Carson, M. C. (2016). A 3D in vitro model of patient-derived prostate cancer xenograft for controlled interrogation of in vivo tumor–stromal interactions. Biomaterials, 77, 164–172. https://doi.org/10.1016/j.biomaterials.2015.10.059
- Gill, B. J., & West, J. L. (2014). Modeling the tumor extracellular matrix: Tissue engineering tools repurposed towards new frontiers in cancer biology. Journal of Biomechanics, 47(9), 1969–1978. https://doi.org/10.1016/j.jbiomech.2013.09.029
- Girotti, M. R., Gremel, G., Lee, R., Galvani, E., Rothwell, D., Viros, A., … Marais, R. (2016). Application of sequencing, liquid biopsies, and patient-derived xenografts for personalized medicine in melanoma. Cancer Discovery, 6(3), 286–299. https://doi.org/10.1158/2159-8290.CD-15-1336
- Godugu, C., Patel, A. R., Desai, U., Andey, T., Sams, A., & Singh, M. (2013). AlgiMatrix (TM) based 3D cell culture system as an in-vitro tumor model for anticancer studies. PLoS ONE, 8(1), e537081. https://doi.org/10.1371/journal.pone.0053708
- Goodspeed, A., Heiser, L. M., Gray, J. W., & Costello, J. C. (2016). Tumor-derived cell lines as molecular models of cancer pharmacogenomics. Molecular Cancer Research, 14(1), 3–13. https://doi.org/10.1158/1541-7786.MCR-15-0189
- Gordon, S., & Taylor, P. R. (2005). Monocyte and macrophage heterogeneity. Nature Reviews Immunology, 5(12), 953–964. https://doi.org/10.1038/nri1733
- Goubko, C. A., & Cao, X. (2009). Patterning multiple cell types in co-cultures: A review. Materials Science and Engineering: C, 29(6), 1855–1868. https://doi.org/10.1016/j.msec.2009.02.016
- Grolman, J. M., Zhang, D., Smith, A. M., Moore, J. S., & Kilian, K. A. (2015). Rapid 3D extrusion of synthetic tumor microenvironments. Advanced Materials, 27(37), 5512–5517. https://doi.org/10.1002/adma.201501729
- Guven, S., Chen, P., Inci, F., Tasoglu, S., Erkmen, B., & Demirci, U. (2015). Multiscale assembly for tissue engineering and regenerative medicine. Trends in Biotechnology, 33(5), 269–279. https://doi.org/10.1016/j.tibtech.2015.02.003
- Ham, S. L., Atefi, E., Fyffe, D., & Tavana, H. (2015). Robotic production of cancer cell spheroids with an aqueous two-phase system for drug testing. JOVE—Journal of Visualized Experiments, (98), e5275498.
- Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell, 144(5), 646–674. https://doi.org/10.1016/j.cell.2011.02.013
- Hao, H., Muniz-Medina, V. M., Mehta, H., Thomas, N. E., Khazak, V., Der, C. J., & Shields, J. M. (2007). Context dependent roles of mutant B-Raf signaling in melanoma and colorectal carcinoma cell growth. Molecular cancer therapeutics, 6(8), 2220–2229.
- Hao, C., Wang, L., Peng, S., Cao, M., Li, H., Hu, J., … Fang, B. (2015). Gene mutations in primary tumors and corresponding patient-derived xenografts derived from non-small cell lung cancer. Cancer Letters, 357(1), 179–185. https://doi.org/10.1016/j.canlet.2014.11.024
- Heinemann, V., Reni, M., Ychou, M., Richel, D. J., Macarulla, T., & Ducreux, M. (2014). Tumour–stroma interactions in pancreatic ductal adenocarcinoma: Rationale and current evidence for new therapeutic strategies. Cancer Treatment Reviews, 40(1), 118–128. https://doi.org/10.1016/j.ctrv.2013.04.004
- Hidalgo, M., Amant, F., Biankin, A. V., Budinska, E., Byrne, A. T., Caldas, C., … Villanueva, A. (2014). Patient-derived xenograft models: An emerging platform for translational cancer research. Cancer Discovery, 4(9), 998–1013. https://doi.org/10.1158/2159-8290.CD-14-0001
- Hirschhaeuser, F., Menne, H., Dittfeld, C., West, J., Mueller-Klieser, W., & Kunz-Schughart, L. A. (2010). Multicellular tumor spheroids: An underestimated tool is catching up again. Journal of Biotechnology, 148(1), 3–15. https://doi.org/10.1016/j.jbiotec.2010.01.012
- Hoelzel, M., Bovier, A., & Tueting, T. (2013). Plasticity of tumour and immune cells: A source of heterogeneity and a cause for therapy resistance? Nature Reviews Cancer, 13(5), 365–395. https://doi.org/10.1038/nrc3498
- Horning, J. L., Sahoo, S. K., Vijayaraghavalu, S., Dimitrijevic, S., Vasir, J. K., Jain, T. K., … Labhasetwar, V. (2008). 3-D tumor model for in vitro evaluation of anticancer drugs. Molecular Pharmaceutics, 5(5), 849–862. https://doi.org/10.1021/mp800047v
- Hotary, K. B., Allen, E. D., Brooks, P. C., Datta, N. S., Long, M. W., & Weiss, A. S. J. (2003). Membrane type I matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix. Cell, 114(1), 33–45. https://doi.org/10.1016/S0092-8674(03)00513-0
- Hsiao, A. Y., Torisawa, Y., Tung, Y., Sud, S., Taichman, R. S., Pienta, K. J., & Takayama, S. (2009). Microfluidic system for formation of PC-3 prostate cancer co-culture spheroids. Biomaterials, 30(16), 3020–3027. https://doi.org/10.1016/j.biomaterials.2009.02.047
- Huang, C. P., Lu, J., Seon, H., Lee, A. P., Flanagan, L. A., Kim, H., … Jeon, N. L. (2009). Engineering microscale cellular niches for three-dimensional multicellular co-cultures. Lab on a Chip, 9(12), 1740. https://doi.org/10.1039/b818401a
- Hyun, K., Lee, T. Y., Lee, S. H., & Jung, H. (2015). Two-stage microfluidic chip for selective isolation of circulating tumor cells (CTCs). Biosensors & Bioelectronics, 67(SI), 86–92.
- Jamal-Hanjani, M., Wilson, G. A., Horswell, S., Mitter, R., Sakarya, O., Constantin, T., … Swanton, C. (2016). Detection of ubiquitous and heterogeneous mutations in cell-free DNA from patients with early-stage non-small-cell lung cancer. Annals of Oncology, 27(5), 862–867. https://doi.org/10.1093/annonc/mdw037
- Jenkinson, S. R., Barraclough, R., West, C. R., & Rudland, P. S. (2004). S100A4 regulates cell motility and invasion in an in vitro model for breast cancer metastasis. BR J Cancer, 90(1), 253–262. https://doi.org/10.1038/sj.bjc.6601483
- Jeong, S., Lee, J., Shin, Y., Chung, S., & Kuh, H. (2016). Co-culture of tumor spheroids and fibroblasts in a collagen matrix-incorporated microfluidic chip mimics reciprocal activation in solid tumor microenvironment. PLoS ONE, 11(7), e01590137. https://doi.org/10.1371/journal.pone.0159013
- Jiang, B., Mason, J., Jewett, A., Liu, M., Chen, W., Qian, J., … Man, Y. (2013). Tumor-infiltrating immune cells: Triggers for tumor capsule disruption and tumor progression? International Journal of Medical Sciences, 10(5), 475–497. https://doi.org/10.7150/ijms.5798
- Jiang, W. G., & Harding, K. G. (1998). Enhancement of wound tissue expansion and angiogenesis by matrix-embedded fibroblast (dermagraft), a role of hepatocyte growth factor/scatter factor. International Journal of Molecular Medicine, 2(2), 203–210.
- Junttila, M. R., & de Sauvage, F. J. (2013). Influence of tumour micro-environment heterogeneity on therapeutic response. Nature, 501(7467), 346–354. https://doi.org/10.1038/nature12626
- Kelland, L. R. (2004). "Of mice and men": Values and liabilities of the athymic nude mouse model in anticancer drug development. European Journal of Cancer, 40(6), 827–836. https://doi.org/10.1016/j.ejca.2003.11.028
- Kievit, F. M., Wang, K., Erickson, A. E., Levengood, S. K. L., Ellenbogen, R. G., & Zhang, M. (2016). Modeling the tumor microenvironment using chitosan-alginate scaffolds to control the stem-like state of glioblastoma cells. Biomaterials Science, 4(4), 610–613. https://doi.org/10.1039/c5bm00514k
- Knowlton, S., Onal, S., Yu, C. H., Zhao, J. J., & Tasoglu, S. (2015). Bioprinting for cancer research. Trends in Biotechnology, 33(9), 504–513. https://doi.org/10.1016/j.tibtech.2015.06.007
- Kolahchi, A. R., Mohtaram, N. K., Modarres, H. P., Mohammadi, M. H., Geraili, A., Jafari, P., … Sanati-Nezhad, A. (2016). Microfluidic-based multi-organ platforms for drug discovery. Micromachines, 7(9), 1629.
- Kolesky, D. B., Truby, R. L., Gladman, A. S., Busbee, T. A., Homan, K. A., & Lewis, J. A. (2014). 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Advanced Materials, 26(19), 3124–3130. https://doi.org/10.1002/adma.201305506
- Konstorum, A., Vella, A. T., Adler, A. J., & Laubenbacher, R. C. (2017). Addressing current challenges in cancer immunotherapy with mathematical and computational modelling. Journal of the Royal Society Interface, 14(131), 20170150131.
- Koontongkaew, S. (2013). The tumor microenvironment contribution to development, growth, invasion and metastasis of head and neck squamous cell carcinomas. Journal of Cancer, 4(1), 66–83. https://doi.org/10.7150/jca.5112
- Kuperwasser, C., Chavarria, T., Wu, M., Magrane, G., Gray, J. W., Carey, L., … Weinberg, R. A. (2004). Reconstruction of functionally normal and malignant human breast tissues in mice. Proceedings of the National Academy of Sciences of the United States of America, 101(14), 4966–4971. https://doi.org/10.1073/pnas.0401064101
- Kwak, B., Lee, J., Lee, D., Lee, K., Kwon, O., Kang, S., & Kim, Y. (2017). Selective isolation of magnetic nanoparticle-mediated heterogeneity subpopulation of circulating tumor cells using magnetic gradient based microfluidic system. Biosensors & Bioelectronics, 88(SI), 153–158.
- LaBarbera, D. V., Reid, B. G., & Yoo, B. H. (2012). The multicellular tumor spheroid model for high-throughput cancer drug discovery. Expert Opinion on Drug Discovery, 7(9), 819–830. https://doi.org/10.1517/17460441.2012.708334
- Lamichhane, S. P., Arya, N., Kohler, E., Xiang, S., Christensen, J., & Shastri, V. P. (2016). Recapitulating epithelial tumor microenvironment in vitro using three dimensional tri-culture of human epithelial, endothelial, and mesenchymal cells. BMC Cancer, 16(1), 581. https://doi.org/10.1186/s12885-016-2634-1
- Lee, V. K., Dai, G., Zou, H., & Yoo, S. S. (2015, April). Generation of 3-D glioblastoma-vascular niche using 3-D bioprinting. In 2015 41st Annual Northeast Biomedical Engineering Conference (NEBEC) (pp. 1–2). IEEE.
10.1109/NEBEC.2015.7117111 Google Scholar
- Leggett, S. E., Khoo, A. S., & Wong, I. Y. (2017). Multicellular tumor invasion and plasticity in biomimetic materials. Biomaterials Science, 5(8), 1460–1479. https://doi.org/10.1039/C7BM00272F
- Li, Y., Chen, P., Wang, Y., Yan, S., Feng, X., Du, W., … Liu, B. (2016). Rapid assembly of heterogeneous 3D cell microenvironments in a microgel array. Advanced Materials, 28(18), 3543–3548. https://doi.org/10.1002/adma.201600247
- Liang, Y., Jeong, J., DeVolder, R. J., Cha, C., Wang, F., Tong, Y. W., & Kong, H. (2011). A cell-instructive hydrogel to regulate malignancy of 3D tumor spheroids with matrix rigidity. Biomaterials, 32(35), 9308–9315. https://doi.org/10.1016/j.biomaterials.2011.08.045
- Lu, W., Zhang, L., Wu, C., Liu, Z., Lei, G., Liu, J., … Hu, Y. (2014). Development of an acellular tumor extracellular matrix as a three-dimensional scaffold for tumor engineering. PLoS ONE, 9(7), e1036727. https://doi.org/10.1371/journal.pone.0103672
- Malda, J., Visser, J., Melchels, F. P., Jüngst, T., Hennink, W. E., Dhert, W. J., … Hutmacher, D. W. (2013). 25th anniversary article: Engineering hydrogels for biofabrication. Advanced Materials, 25(36), 5011–5028. https://doi.org/10.1002/adma.201302042
- Manz, M. G. (2007). Human-hemato-lymphoid-system mice: Opportunities and challenges. Immunity, 26(5), 537–541. https://doi.org/10.1016/j.immuni.2007.05.001
- Meacham, C. E., & Morrison, S. J. (2013). Tumour heterogeneity and cancer cell plasticity. Nature, 501(7467), 328–337. https://doi.org/10.1038/nature12624
- Mehta, G., Hsiao, A. Y., Ingram, M., Luker, G. D., & Takayama, S. (2012). Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy. Journal of Controlled Release, 164(2), 192–204. https://doi.org/10.1016/j.jconrel.2012.04.045
- Mei, Z., Boughton, P., Rose, B., Lee, C. S., & Hong, A. M. (2013). The use of porous scaffold as a tumor model. International Journal of Biomaterials, XXX, 396056–396059. https://doi.org/10.1155/2013/396056
10.1155/2013/396056 Google Scholar
- Mi, S., Liu, Z., Du, Z., Yi, X., & Sun, W. (2019). Three-dimensional microfluidic tumor–macrophage system for breast cancer cell invasion. Biotechnology and Bioengineering, 116(7), 1731–1741. https://doi.org/10.1002/bit.26961
- Mittler, F., Obeïd, P., Rulina, A. V., Haguet, V., Gidrol, X., & Balakirev, M. Y. (2017). High-content monitoring of drug effects in a 3D spheroid model. Frontiers in Oncology, 7, 293. https://doi.org/10.3389/fonc.2017.00293
- Mohanty, A. K., Datta, A., & Venkatraj, V. (2016). A conjugate exponential model for cancer tissue heterogeneity. IEEE Journal of Biomedical and Health Informatics, 20(2), 699–709. https://doi.org/10.1109/JBHI.2015.2410279
- Niu, Y., Bai, J., Kamm, R. D., Wang, Y., & Wang, C. (2014). Validating antimetastatic effects of natural products in an engineered microfluidic platform mimicking tumor microenvironment. Molecular Pharmaceutics, 11(7), 2022–2029. https://doi.org/10.1021/mp500054h
- Nyga, A., Cheema, U., & Loizidou, M. (2011). 3D tumour models: Novel in vitro approaches to cancer studies. Journal of Cell Communication and Signaling, 5(3), 239–248. https://doi.org/10.1007/s12079-011-0132-4
- Okochi, M., Takano, S., Isaji, Y., Senga, T., Hamaguchi, M., & Honda, H. (2009). Three-dimensional cell culture array using magnetic force-based cell patterning for analysis of invasive capacity of BALB/3T3/v-src. Lab on a Chip, 9(23), 3378–3384. https://doi.org/10.1039/b909304d
- Ong, S., Zhao, Z., Arooz, T., Zhao, D., Zhang, S., Du, T., … Yu, H. (2010). Engineering a scaffold-free 3D tumor model for in vitro drug penetration studies. Biomaterials, 31(6), 1180–1190. https://doi.org/10.1016/j.biomaterials.2009.10.049
- Ostrand-Rosenberg, S. (2004). Animal models of tumor immunity, immunotherapy and cancer vaccines. Current Opinion in Immunology, 16(2), 143–150. https://doi.org/10.1016/j.coi.2004.01.003
- Palladini, A., Nicoletti, G., Pappalardo, F., Murgo, A., Grosso, V., Stivani, V., … Lollini, P. (2010). In silico modeling and in vivo efficacy of cancer-preventive vaccinations. Cancer Research, 70(20), 7755–7763. https://doi.org/10.1158/0008-5472.CAN-10-0701
- Park, H., Cho, S., Kang, W., Han, J. Y., Mi, S., Kang, J., … Park, H. (2016). An integrative approach to precision cancer medicine using patient-derived xenografts. Molecules and Cells, 39(2), 77–86.
- Patel, D., Gao, Y., Son, K., Siltanen, C., Neve, R. M., Ferrara, K., & Revzin, A. (2015). Microfluidic co-cultures with hydrogel-based ligand trap to study paracrine signals giving rise to cancer drug resistance. Lab on a Chip, 15(24), 4614–4624. https://doi.org/10.1039/C5LC00948K
- Peck, Y., & Wang, D. A. (2013). Three-dimensionally engineered biomimetic tissue models for in vitro drug evaluation: Delivery, efficacy and toxicity. Expert Opin Drug Deliv, 10(3), 369–383. https://doi.org/10.1517/17425247.2013.751096
- Phamduy, T. B., Sweat, R. S., Azimi, M. S., Burow, M. E., Murfee, W. L., & Chrisey, D. B. (2015). Printing cancer cells into intact microvascular networks: A model for investigating cancer cell dynamics during angiogenesis. Integrative Biology, 7(9), 1068–1078. https://doi.org/10.1039/C5IB00151J
- Phan-Lai, V., Florczyk, S. J., Kievit, F. M., Wang, K., Gad, E., Disis, M. L., & Zhang, M. (2013). Three-dimensional scaffolds to evaluate tumor associated fibroblast-mediated suppression of breast tumor specific T cells. Biomacromolecules, 14(5), 1330–1337. https://doi.org/10.1021/bm301928u
- Pharoah, P., Dunning, A. M., Ponder, B., & Easton, D. F. (2004). Association studies for finding cancer-susceptibility genetic variants. Nature Reviews Cancer, 4(11), 850–860. https://doi.org/10.1038/nrc1476
- Pickup, M., Novitskiy, S., & Moses, H. L. (2013). The roles of TGF beta in the tumour microenvironment. Nature Reviews Cancer, 13(11), 788–799. https://doi.org/10.1038/nrc3603
- Poulin, P., Chen, Y., Ding, X., Gould, S. E., Hop, C. E., Messick, K., … Liederer, B. M. (2015). Prediction of drug distribution in subcutaneous xenografts of human tumor cell lines and healthy tissues in mouse: Application of the tissue composition–based model to antineoplastic drugs. Journal of Pharmaceutical Sciences, 104(4), 1508–1521. https://doi.org/10.1002/jps.24336
- Prestwich, G. D. (2008). Evaluating drug efficacy and toxicology in three dimensions: Using synthetic extracellular matrices in drug discovery. Accounts of Chemical Research, 41(1), 139–148. https://doi.org/10.1021/ar7000827
- Regier, M. C., Maccoux, L. J., Weinberger, E. M., Regehr, K. J., Berry, S. M., Beebe, D. J., & Alarid, E. T. (2016). Transitions from mono- to co- to tri-culture uniquely affect gene expression in breast cancer, stromal, and immune compartments. Biomedical Microdevices, 18(4), 70. https://doi.org/10.1007/s10544-016-0083-x
- Rodenhizer, D., Gaude, E., Cojocari, D., Mahadevan, R., Frezza, C., Wouters, B. G., & McGuigan, A. P. (2016). A three-dimensional engineered tumour for spatial snapshot analysis of cell metabolism and phenotype in hypoxic gradients (vol 15, pg 227, 2016). Nature Materials, 15(2), 244. https://doi.org/10.1038/nmat4515
- Sabhachandani, P., Motwani, V., Cohen, N., Sarkar, S., Torchilin, V., & Konry, T. (2016). Generation and functional assessment of 3D multicellular spheroids in droplet based microfluidics platform. Lab on a Chip, 16(3), 497–505. https://doi.org/10.1039/C5LC01139F
- Santo, V. E., Estrada, M. F., Rebelo, S. P., Abreu, S., Silva, I., Pinto, C., … Brito, C. (2016). Adaptable stirred-tank culture strategies for large scale production of multicellular spheroid-based tumor cell models. Journal of Biotechnology, 221, 118–129. https://doi.org/10.1016/j.jbiotec.2016.01.031
- Sarioglu, A. F., Aceto, N., Kojic, N., Donaldson, M. C., Zeinali, M., Hamza, B., … Toner, M. (2015). A microfluidic device for label-free, physical capture of circulating tumor cell clusters. Nature Methods, 12(7), 685–691. https://doi.org/10.1038/NMETH.3404
- Schumacher, D., Andrieux, G., Boehnke, K., Keil, M., Silvestri, A., Silvestrov, M., … Templin, M. (2019). Heterogeneous pathway activation and drug response modelled in colorectal-tumor–derived 3D cultures. PLoS Genetics, 15(3), e1008076. https://doi.org/10.1371/journal.pgen.1008076
- Shultz, L. D., Ishikawa, F., & Greiner, D. L. (2007). Humanized mice in translational biomedical research. Nature Reviews Immunology, 7(2), 118–130. https://doi.org/10.1038/nri2017
- Siegel, R. L., Miller, K. D., & Jemal, A. (2019). Cancer statistics, 2019. CA—A Cancer Journal for Clinicians, 69(1), 7–34. https://doi.org/10.3322/caac.21551
- Siolas, D., & Hannon, G. J. (2013). Patient-derived tumor xenografts: Transforming clinical samples into mouse models. Cancer Research, 73(17), 5315–5319. https://doi.org/10.1158/0008-5472.CAN-13-1069
- Skardal, A., & Atala, A. (2015). Biomaterials for integration with 3-D bioprinting. Annals of Biomedical Engineering, 43(3), 730–746. https://doi.org/10.1007/s10439-014-1207-1
- Song, J. W., Cavnar, S. P., Walker, A. C., Luker, K. E., Gupta, M., Tung, Y. C., … Takayama, S. (2009). Microfluidic endothelium for studying the intravascular adhesion of metastatic breast cancer cells. PloS one, 4(6), e5756.
- Song, H. G., Park, K. M., & Gerecht, S. (2014). Hydrogels to model 3D in vitro microenvironment of tumor vascularization. Advanced Drug Delivery Reviews, 79-80, 19–29. https://doi.org/10.1016/j.addr.2014.06.002
- Spill, F., Reynolds, D. S., Kamm, R. D., & Zaman, M. H. (2016). Impact of the physical microenvironment on tumor progression and metastasis. Current Opinion in Biotechnology, 40, 41–48. https://doi.org/10.1016/j.copbio.2016.02.007
- Spiridon, C. I., Ghetie, M. A., Uhr, J., Marches, R., Li, J. L., Shen, G. L., & Vitetta, E. S. (2002). Targeting multiple Her-2 epitopes with monoclonal antibodies results in improved antigrowth activity of a human breast cancer cell line in vitro and in vivo. Clinical Cancer Research, 8(6), 1720–1730.
- Szade, K., Zukowska, M., Szade, A., Collet, G., Kloska, D., Kieda, C., … Dulak, J. (2016). Spheroid-plug model as a tool to study tumor development, angiogenesis, and heterogeneity in vivo. Tumor Biology, 37(2), 2481–2496. https://doi.org/10.1007/s13277-015-4065-z
- Szot, C. S., Buchanan, C. F., Freeman, J. W., & Rylander, M. N. (2011). 3D in vitro bioengineered tumors based on collagen I hydrogels. Biomaterials, 32(31), 7905–7912. https://doi.org/10.1016/j.biomaterials.2011.07.001
- Tang, L., van de Ven, A. L., Guo, D., Andasari, V., Cristini, V., Li, K. C., & Zhou, X. (2014). Computational modeling of 3D tumor growth and angiogenesis for chemotherapy evaluation. PLoS ONE, 9(1), e83962. https://doi.org/10.1371/journal.pone.0083962
- Tasoglu, S., & Demirci, U. (2013). Bioprinting for stem cell research. Trends in Biotechnology, 31(1), 10–19. https://doi.org/10.1016/j.tibtech.2012.10.005
- Thoma, C. R., Stroebel, S., Roesch, N., Calpe, B., Krek, W., & Kelm, J. M. (2013). A high-throughput-compatible 3D microtissue co-culture system for phenotypic RNAi screening applications. Journal of Biomolecular Screening, 18(10SI), 1330–1337. https://doi.org/10.1177/1087057113499071
- Thoma, C. R., Zimmermann, M., Agarkova, I., Kelm, J. M., & Krek, W. (2014). 3D cell culture systems modeling tumor growth determinants in cancer target discovery. Advanced Drug Delivery Reviews, 69, 29–41. https://doi.org/10.1016/j.addr.2014.03.001
- Ulvmar, M. H., & Makinen, T. (2016). Heterogeneity in the lymphatic vascular system and its origin. Cardiovascular Research, 111(4), 310–321. https://doi.org/10.1093/cvr/cvw175
- Vargo-Gogola, T., & Rosen, J. M. (2007). Modelling breast cancer: One size does not fit all. Nature Reviews Cancer, 7(9), 659–672. https://doi.org/10.1038/nrc2193
- Verjans, E. T., Doijen, J., Luyten, W., Landuyt, B., & Schoofs, L. (2018). Three-dimensional cell culture models for anticancer drug screening: Worth the effort? Journal of Cellular Physiology, 233(4), 2993–3003. https://doi.org/10.1002/jcp.26052
- Vinci, M., Gowan, S., Boxall, F., Patterson, L., Zimmermann, M., Court, W., … Eccles, S. A. (2012). Advances in establishment and analysis of three-dimensional tumor spheroid–based functional assays for target validation and drug evaluation. BMC Biology, 10(1), 29. https://doi.org/10.1186/1741-7007-10-29
- Waclaw, B., Bozic, I., Pittman, M. E., Hruban, R. H., Vogelstein, B., & Nowak, M. A. (2015). A spatial model predicts that dispersal and cell turnover limit intratumour heterogeneity. Nature, 525(7568), 261–264. https://doi.org/10.1038/nature14971
- Wang, C., Tang, Z., Zhao, Y., Yao, R., Li, L., & Sun, W. (2014). Three-dimensional in vitro cancer models: A short review. Biofabrication, 6(2), 22001. https://doi.org/10.1088/1758-5082/6/2/022001
- Wang, D. C., & Wang, X. (2017). Systems heterogeneity: An integrative way to understand cancer heterogeneity. Seminars in Cell & Developmental Biology, 64, 1–4. https://doi.org/10.1016/j.semcdb.2016.08.016
- Wang, J., Zhu, Y., Ma, H., Chen, S., Chao, J., Ruan, W., … Meng, Y. (2016). Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. Materials Science and Engineering: C, 62, 215–225. https://doi.org/10.1016/j.msec.2016.01.045
- Weis, S. M., & Cheresh, D. A. (2011). Tumor angiogenesis: Molecular pathways and therapeutic targets. Nature Medicine, 17(11), 1359–1370. https://doi.org/10.1038/nm.2537
- Weiswald, L., Bellet, D., & Dangles-Marie, V. (2015). Spherical cancer models in tumor biology. Neoplasia, 17(1), 1–15. https://doi.org/10.1016/j.neo.2014.12.004
- Wells, D. K., Chuang, Y., Knapp, L. M., Brockmann, D., Kath, W. L., & Leonard, J. N. (2015). Spatial and functional heterogeneities shape collective behavior of tumor-immune networks. PLoS Computational Biology, 11(4), e1004181. https://doi.org/10.1371/journal.pcbi.1004181
- Whittle, J. R., Lewis, M. T., Lindeman, G. J., & Visvader, J. E. (2015). Patient-derived xenograft models of breast cancer and their predictive power. Breast Cancer Research, 17(17). https://doi.org/10.1186/s13058-015-0523-1
- Willey, C. D., Gilbert, A. N., Anderson, J. C., & Gillespie, G. Y. (2015). Patient-derived xenografts as a model system for radiation research. Seminars in Radiation Oncology, 25(4), 273–280. https://doi.org/10.1016/j.semradonc.2015.05.008
- Wu, M., Frieboes, H. B., McDougall, S. R., Chaplain, M. A. J., Cristini, V., & Lowengrub, J. (2013). The effect of interstitial pressure on tumor growth: Coupling with the blood and lymphatic vascular systems. Journal of Theoretical Biology, 320, 131–151. https://doi.org/10.1016/j.jtbi.2012.11.031
- Wu, M., & Swartz, M. A. (2014). Modeling tumor microenvironments in vitro. Journal of Biomechanical Engineering—Transactions of the ASME, 136(2), 021011.
- Xu, F., Celli, J., Rizvi, I., Moon, S., Hasan, T., & Demirci, U. (2011). A three-dimensional in vitro ovarian cancer coculture model using a high-throughput cell patterning platform. Biotechnology Journal, 6(2), 204–212. https://doi.org/10.1002/biot.201000340
- Xu, X., Farach-Carson, M. C., & Jia, X. (2014). Three-dimensional in vitro tumor models for cancer research and drug evaluation. Biotechnology Advances, 32(7), 1256–1268. https://doi.org/10.1016/j.biotechadv.2014.07.009
- Xu, X., Gurski, L. A., Zhang, C., Harrington, D. A., Farach-Carson, M. C., & Jia, X. (2012). Recreating the tumor microenvironment in a bilayer, hyaluronic acid hydrogel construct for the growth of prostate cancer spheroids. Biomaterials, 33(35), 9049–9060. https://doi.org/10.1016/j.biomaterials.2012.08.061
- Xu, Z., Gao, Y., Hao, Y., Li, E., Wang, Y., Zhang, J., … Wang, Q. (2013). Application of a microfluidic chip-based 3D co-culture to test drug sensitivity for individualized treatment of lung cancer. Biomaterials, 34(16), 4109–4117. https://doi.org/10.1016/j.biomaterials.2013.02.045
- Yamazoe, H., Ichikawa, T., Hagihara, Y., & Iwasaki, Y. (2016). Generation of a patterned co-culture system composed of adherent cells and immobilized nonadherent cells. Acta Biomaterialia, 31, 231–240. https://doi.org/10.1016/j.actbio.2015.12.016
- Yao, R., Wang, J., Li, X., Da, J., Qi, H., Kee, K. K., & Du, Y. (2014). Hepatic differentiation of human embryonic stem cells as microscaled multilayered colonies leading to enhanced homogeneity and maturation. Small, XXX, XXX, n/a-n/a. https://doi.org/10.1002/smll.201401040
- Yao, R., Zhang, R., Lin, F., & Luan, J. (2013). Biomimetic injectable HUVEC-adipocytes/collagen/alginate microsphere co-cultures for adipose tissue engineering. Biotechnology and Bioengineering, 110(5), 1430–1443. https://doi.org/10.1002/bit.24784
- Yip, D., & Cho, C. H. (2013). A multicellular 3D heterospheroid model of liver tumor and stromal cells in collagen gel for anti-cancer drug testing. Biochemical and Biophysical Research Communications, 433(3), 327–332. https://doi.org/10.1016/j.bbrc.2013.03.008
- Zanoni, M., Pignatta, S., Arienti, C., Bonafè, M., & Tesei, A. (2019). Anticancer drug discovery using multicellular tumor spheroid models. Expert Opinion on Drug Discovery, 14(3), 289–301.
- Zervantonakis, I. K., Hughes-Alford, S. K., Charest, J. L., Condeelis, J. S., Gertler, F. B., & Kamm, R. D. (2012). Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function. Proceedings of the National Academy of Sciences of the United States of America, 109(34), 13515–13520. https://doi.org/10.1073/pnas.1210182109
- Zhang, W., Lee, W. Y., Siegel, D. S., Tolias, P., & Zilberberg, J. (2014). Patient-specific 3D microfluidic tissue model for multiple myeloma. Tissue Engineering Part C: Methods, 20(8), 663–670. https://doi.org/10.1089/ten.tec.2013.0490
- Zhang, Z., & Nagrath, S. (2013). Microfluidics and cancer: Are we there yet? Biomedical Microdevices, 15(4), 595–609. https://doi.org/10.1007/s10544-012-9734-8
- Zhao, Y., Li, Y., Mao, S., Sun, W., & Yao, R. (2015). The influence of printing parameters on cell survival rate and printability in microextrusion-based 3D cell printing technology. Biofabrication, 7(0450024). https://doi.org/10.1088/1758-5090/7/4/045002
10.1088/1758?5090/7/4/045002 Google Scholar
- Zhao, Y., Yao, R., Ouyang, L., Ding, H., Zhang, T., Zhang, K., … Sun, W. (2014). Three-dimensional printing of Hela cells for cervical tumor model in vitro. Biofabrication, 6(3), 0350013.
- Zheng, C., Zhao, L., Chen, G. E., Zhou, Y., Pang, Y., & Huang, Y. (2012). Quantitative study of the dynamic tumor–endothelial cell interactions through an integrated microfluidic coculture system. Analytical Chemistry, 84(4), 2088–2093. https://doi.org/10.1021/ac2032029
- Zheng, M., Wang, J., Chen, Y., Xu, L., Xue, D., Fu, W., … Wang, S. (2012). A novel mouse model of gastric cancer with human gastric microenvironment. Cancer Letters, 325(1), 108–115. https://doi.org/10.1016/j.canlet.2012.06.011
- Zhu, W., Holmes, B., Glazer, R. I., & Zhang, L. G. (2016). 3D printed nanocomposite matrix for the study of breast cancer bone metastasis. Nanomedicine-Nanotechnology Biology and Medicine, 12(1), 69–79. https://doi.org/10.1016/j.nano.2015.09.010
