1932

Abstract

Cancer models strive to recapitulate the incredible diversity inherent in human tumors. A key challenge in accurate tumor modeling lies in capturing the panoply of homo- and heterotypic cellular interactions within the context of a three-dimensional tissue microenvironment. To address this challenge, researchers have developed organotypic cancer models (organoids) that combine the 3D architecture of in vivo tissues with the experimental facility of 2D cell lines. Here we address the benefits and drawbacks of these systems, as well as their most recent advances. In particular, we focus on the application of such models to the discovery of novel cancer drivers, the study of tumor biology, and the development of novel therapeutic approaches for the treatment of cancer.

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2016-05-23
2024-06-24
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Literature Cited

  1. Boehm JS, Hahn WC. 1.  2011. Towards systematic functional characterization of cancer genomes. Nat. Rev. Genet. 12:487–98 [Google Scholar]
  2. Leighton J, Kline I, Belkin M, Legallais F, Orr HC. 2.  1957. The similarity in histologic appearance of some human cancer and normal cell strains in sponge-matrix tissue culture. Cancer Res. 17:359–63 [Google Scholar]
  3. Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA. 3.  et al. 2012. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483:603–7 [Google Scholar]
  4. Egeblad M, Nakasone ES, Werb Z. 4.  2010. Tumors as organs: complex tissues that interface with the entire organism. Dev. Cell 18:884–901 [Google Scholar]
  5. Fischbach C, Chen R, Matsumoto T, Schmelzle T, Brugge JS. 5.  et al. 2007. Engineering tumors with 3D scaffolds. Nat. Methods 4:855–60 [Google Scholar]
  6. Infanger DW, Lynch ME, Fischbach C. 6.  2013. Engineered culture models for studies of tumor-microenvironment interactions. Annu. Rev. Biomed. Eng. 15:29–53 [Google Scholar]
  7. Yeung TM, Gandhi SC, Bodmer WF. 7.  2011. Hypoxia and lineage specification of cell line-derived colorectal cancer stem cells. PNAS 108:4382–87 [Google Scholar]
  8. Yeung TM, Gandhi SC, Wilding JL, Muschel R, Bodmer WF. 8.  2010. Cancer stem cells from colorectal cancer-derived cell lines. PNAS 107:3722–27 [Google Scholar]
  9. DuPage M, Jacks T. 9.  2013. Genetically engineered mouse models of cancer reveal new insights about the antitumor immune response. Curr. Opin. Immunol. 25:192–99 [Google Scholar]
  10. Amos-Landgraf JM, Kwong LN, Kendziorski CM, Reichelderfer M, Torrealba J. 10.  et al. 2007. A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer. PNAS 104:4036–41 [Google Scholar]
  11. Neal JT, Peterson TS, Kent ML, Guillemin K. 11.  2013. H. pylori virulence factor CagA increases intestinal cell proliferation by Wnt pathway activation in a transgenic zebrafish model. Dis. Model. Mech. 6:802–10 [Google Scholar]
  12. Gateff E. 12.  1978. Malignant neoplasms of genetic origin in Drosophila melanogaster. Science 200:1448–59 [Google Scholar]
  13. Giovanella BC, Yim SO, Stehlin JS, Williams LJ Jr. 13.  1972. Development of invasive tumors in the “nude” mouse after injection of cultured human melanoma cells. J. Natl. Cancer Inst. 48:1531–33 [Google Scholar]
  14. Rygaard J, Povlsen CO. 14.  1969. Heterotransplantation of a human malignant tumour to “Nude” mice. Acta Pathol. Microbiol. Scand. 77:758–60 [Google Scholar]
  15. Chen JM. 15.  1954. The cultivation in fluid medium of organised liver, pancreas and other tissues of foetal rats. Exp. Cell Res. 7:518–29 [Google Scholar]
  16. O'Brien LE, Zegers MM, Mostov KE. 16.  2002. Building epithelial architecture: insights from three-dimensional culture models. Nat. Rev. Mol. Cell Biol. 3:531–37 [Google Scholar]
  17. Li X, Nadauld L, Ootani A, Corney DC, Pai RK. 17.  et al. 2014. Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture. Nat. Med. 20:769–77 [Google Scholar]
  18. Sato T, Stange DE, Ferrante M, Vries RG. Van Es JH. 18.  et al. 2011. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology 141:1762–72 [Google Scholar]
  19. Eiraku M, Watanabe K, Matsuo-Takasaki M, Kawada M, Yonemura S. 20.  et al. 2008. Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell 3:519–32 [Google Scholar]
  20. Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS. 21.  et al. 2013. Cerebral organoids model human brain development and microcephaly. Nature 501:373–79 [Google Scholar]
  21. Shamir ER, Pappalardo E, Jorgens DM, Coutinho K, Tsai WT. 22.  et al. 2014. Twist1-induced dissemination preserves epithelial identity and requires E-cadherin. J. Cell Biol. 204:839–56 [Google Scholar]
  22. Simian M, Hirai Y, Navre M, Werb Z, Lochter A, Bissell MJ. 23.  2001. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells. Development 128:3117–31 [Google Scholar]
  23. Kovbasnjuk O, Zachos NC, In J, Foulke-Abel J, Ettayebi K. 24.  et al. 2013. Human enteroids: preclinical models of non-inflammatory diarrhea. Stem Cell Res. Ther. 4:Suppl. 1S3 [Google Scholar]
  24. Ootani A, Li X, Sangiorgi E, Ho QT, Ueno H. 25.  et al. 2009. Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat. Med. 15:701–6 [Google Scholar]
  25. Eiraku M, Takata N, Ishibashi H, Kawada M, Sakakura E. 26.  et al. 2011. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472:51–56 [Google Scholar]
  26. Kalabis J, Wong GS, Vega ME, Natsuizaka M, Robertson ES. 27.  et al. 2012. Isolation and characterization of mouse and human esophageal epithelial cells in 3D organotypic culture. Nat. Protoc. 7:235–46 [Google Scholar]
  27. Qiao J, Sakurai H, Nigam SK. 28.  1999. Branching morphogenesis independent of mesenchymal-epithelial contact in the developing kidney. PNAS 96:7330–35 [Google Scholar]
  28. Zhang X, Bush KT, Nigam SK. 29.  2012. In vitro culture of embryonic kidney rudiments and isolated ureteric buds. Methods Mol. Biol. 886:13–21 [Google Scholar]
  29. Huch M, Gehart H, van Boxtel R, Hamer K, Blokzijl F. 30.  et al. 2015. Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160:299–312 [Google Scholar]
  30. Takebe T, Sekine K, Enomura M, Koike H, Kimura M. 31.  et al. 2013. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499:481–84 [Google Scholar]
  31. Liu Y, Stein E, Oliver T, Li Y, Brunken WJ. 32.  et al. 2004. Novel role for Netrins in regulating epithelial behavior during lung branching morphogenesis. Curr. Biol. 14:897–905 [Google Scholar]
  32. Rock JR, Onaitis MW, Rawlins EL, Lu Y, Clark CP. 33.  et al. 2009. Basal cells as stem cells of the mouse trachea and human airway epithelium. PNAS 106:12771–75 [Google Scholar]
  33. Huch M, Bonfanti P, Boj SF, Sato T, Loomans CJ. 34.  et al. 2013. Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis. EMBO J. 32:2708–21 [Google Scholar]
  34. Wescott MP, Rovira M, Reichert M, von Burstin J, Means A. 35.  et al. 2009. Pancreatic ductal morphogenesis and the Pdx1 homeodomain transcription factor. Mol. Biol. Cell 20:4838–44 [Google Scholar]
  35. Barker N, Huch M, Kujala P, van de Wetering M, Snippert HJ. 36.  et al. 2010. Lgr5+ve stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6:25–36 [Google Scholar]
  36. Stange DE, Koo BK, Huch M, Sibbel G, Basak O. 37.  et al. 2013. Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium. Cell 155:357–68 [Google Scholar]
  37. Hynds RE, Giangreco A. 38.  2013. Concise review: the relevance of human stem cell-derived organoid models for epithelial translational medicine. Stem Cells 31:417–22 [Google Scholar]
  38. Lancaster MA, Knoblich JA. 39.  2014. Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345:1247125 [Google Scholar]
  39. Shamir ER, Ewald AJ. 40.  2014. Three-dimensional organotypic culture: experimental models of mammalian biology and disease. Nat. Rev. Mol. Cell Biol. 15:647–64 [Google Scholar]
  40. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N. 41.  et al. 2009. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459:262–65 [Google Scholar]
  41. Kleinman HK, Martin GR. 42.  2005. Matrigel: basement membrane matrix with biological activity. Semin. Cancer Biol. 15:378–86 [Google Scholar]
  42. Stelzner M, Helmrath M, Dunn JC, Henning SJ, Houchen CW. 43.  et al. 2012. A nomenclature for intestinal in vitro cultures. Am. J. Physiol. Gastrointest. Liver Physiol. 302:G1359–63 [Google Scholar]
  43. Lahar N, Lei NY, Wang J, Jabaji Z, Tung SC. 44.  et al. 2011. Intestinal subepithelial myofibroblasts support in vitro and in vivo growth of human small intestinal epithelium. PLOS ONE 6:e26898 [Google Scholar]
  44. Yin X, Farin HF, van Es JH, Clevers H, Langer R, Karp JM. 45.  2014. Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their progeny. Nat. Methods 11:106–12 [Google Scholar]
  45. Jung P, Sato T, Merlos-Suarez A, Barriga FM, Iglesias M. 46.  et al. 2011. Isolation and in vitro expansion of human colonic stem cells. Nat. Med. 17:1225–27 [Google Scholar]
  46. Wang F, Scoville D, He XC, Mahe MM, Box A. 47.  et al. 2013. Isolation and characterization of intestinal stem cells based on surface marker combinations and colony-formation assay. Gastroenterology 145:383–95 [Google Scholar]
  47. Gracz AD, Fuller MK, Wang F, Li L, Stelzner M. 48.  et al. 2013. Brief report: CD24 and CD44 mark human intestinal epithelial cell populations with characteristics of active and facultative stem cells. Stem Cells 31:2024–30 [Google Scholar]
  48. Karthaus WR, Iaquinta PJ, Drost J, Gracanin A, van Boxtel R. 49.  et al. 2014. Identification of multipotent luminal progenitor cells in human prostate organoid cultures. Cell 159:163–75 [Google Scholar]
  49. Chua CW, Shibata M, Lei M, Toivanen R, Barlow LJ. 50.  et al. 2014. Single luminal epithelial progenitors can generate prostate organoids in culture. Nat. Cell Biol. 16:951–61 [Google Scholar]
  50. Rowe RG, Weiss SJ. 51.  2008. Breaching the basement membrane: who, when and how?. Trends Cell Biol. 18:560–74 [Google Scholar]
  51. Nguyen-Ngoc KV, Ewald AJ. 52.  2013. Mammary ductal elongation and myoepithelial migration are regulated by the composition of the extracellular matrix. J. Microsc. 251:212–23 [Google Scholar]
  52. Nguyen-Ngoc KV, Cheung KJ, Brenot A, Shamir ER, Gray RS. 53.  et al. 2012. ECM microenvironment regulates collective migration and local dissemination in normal and malignant mammary epithelium. PNAS 109:E2595–604 [Google Scholar]
  53. DiMarco RL, Su J, Yan KS, Dewi R, Kuo CJ, Heilshorn SC. 54.  2014. Engineering of three-dimensional microenvironments to promote contractile behavior in primary intestinal organoids. Integr. Biol. 6:127–42 [Google Scholar]
  54. Katano T, Ootani A, Mizoshita T, Tanida S, Tsukamoto H. 55.  et al. 2013. Establishment of a long-term three-dimensional primary culture of mouse glandular stomach epithelial cells within the stem cell niche. Biochem. Biophys. Res. Commun. 432:558–63 [Google Scholar]
  55. Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE. 56.  et al. 2011. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470:105–9 [Google Scholar]
  56. McCracken KW, Howell JC, Wells JM, Spence JR. 57.  2011. Generating human intestinal tissue from pluripotent stem cells in vitro. Nat. Protoc. 6:1920–28 [Google Scholar]
  57. McCracken KW, Cata EM, Crawford CM, Sinagoga KL, Schumacher M. 58.  et al. 2014. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature 516:400–4 [Google Scholar]
  58. Dye BR, Hill DR, Ferguson MA, Tsai YH, Nagy MS. 59.  et al. 2015. In vitro generation of human pluripotent stem cell derived lung organoids. eLife 4:e05098 [Google Scholar]
  59. Suprynowicz FA, Upadhyay G, Krawczyk E, Kramer SC, Hebert JD. 60.  et al. 2012. Conditionally reprogrammed cells represent a stem-like state of adult epithelial cells. PNAS 109:20035–40 [Google Scholar]
  60. Liu X, Ory V, Chapman S, Yuan H, Albanese C. 61.  et al. 2012. ROCK inhibitor and feeder cells induce the conditional reprogramming of epithelial cells. Am. J. Pathol. 180:599–607 [Google Scholar]
  61. Hanahan D, Weinberg RA. 62.  2000. The hallmarks of cancer. Cell 100:57–70 [Google Scholar]
  62. Hanahan D, Weinberg RA. 63.  2011. Hallmarks of cancer: the next generation. Cell 144:646–74 [Google Scholar]
  63. Grabinger T, Luks L, Kostadinova F, Zimberlin C, Medema JP. 64.  et al. 2014. Ex vivo culture of intestinal crypt organoids as a model system for assessing cell death induction in intestinal epithelial cells and enteropathy. Cell Death Dis. 5:e1228 [Google Scholar]
  64. Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X. 65.  et al. 2015. Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat. Genet. 47:320–29 [Google Scholar]
  65. Shultz LD, Goodwin N, Ishikawa F, Hosur V, Lyons BL, Greiner DL. 66.  2014. Human cancer growth and therapy in immunodeficient mouse models. Cold Spring Harb. Protoc. 2014:694–708 [Google Scholar]
  66. Kwong J, Chan FL, Wong KK, Birrer MJ, Archibald KM. 67.  et al. 2009. Inflammatory cytokine tumor necrosis factor α confers precancerous phenotype in an organoid model of normal human ovarian surface epithelial cells. Neoplasia 11:529–41 [Google Scholar]
  67. Matano M, Date S, Shimokawa M, Takano A, Fujii M. 68.  et al. 2015. Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat. Med. 21:256–62 [Google Scholar]
  68. Bas T, Augenlicht LH. 69.  2014. Real time analysis of metabolic profile in ex vivo mouse intestinal crypt organoid cultures. J. Vis. Exp. 93:e52026 [Google Scholar]
  69. Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA. 70.  1999. Creation of human tumour cells with defined genetic elements. Nature 400:464–68 [Google Scholar]
  70. Hahn WC, Weinberg RA. 71.  2002. Rules for making human tumor cells. N. Engl. J. Med. 347:1593–603 [Google Scholar]
  71. Lundberg AS, Randell SH, Stewart SA, Elenbaas B, Hartwell KA. 72.  et al. 2002. Immortalization and transformation of primary human airway epithelial cells by gene transfer. Oncogene 21:4577–86 [Google Scholar]
  72. Sato M, Vaughan MB, Girard L, Peyton M, Lee W. 73.  et al. 2006. Multiple oncogenic changes (K-RASV12, p53 knockdown, mutant EGFRs, p16 bypass, telomerase) are not sufficient to confer a full malignant phenotype on human bronchial epithelial cells. Cancer Res. 66:2116–28 [Google Scholar]
  73. Sasai K, Sukezane T, Yanagita E, Nakagawa H, Hotta A. 74.  et al. 2011. Oncogene-mediated human lung epithelial cell transformation produces adenocarcinoma phenotypes in vivo. Cancer Res. 71:2541–49 [Google Scholar]
  74. Leung CT, Brugge JS. 75.  2012. Outgrowth of single oncogene-expressing cells from suppressive epithelial environments. Nature 482:410–13 [Google Scholar]
  75. Koo BK, Stange DE, Sato T, Karthaus W, Farin HF. 76.  et al. 2012. Controlled gene expression in primary Lgr5 organoid cultures. Nat. Methods 9:81–83 [Google Scholar]
  76. Schwank G, Koo BK, Sasselli V, Dekkers JF, Heo I. 77.  et al. 2013. Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell 13:653–58 [Google Scholar]
  77. Schwank G, Andersson-Rolf A, Koo BK, Sasaki N, Clevers H. 78.  2013. Generation of BAC transgenic epithelial organoids. PLOS ONE 8:e76871 [Google Scholar]
  78. Boj SF, Hwang CI, Baker LA, Chio II, Engle DD. 79.  et al. 2015. Organoid models of human and mouse ductal pancreatic cancer. Cell 160:324–38 [Google Scholar]
  79. Fearon ER, Vogelstein B. 80.  1990. A genetic model for colorectal tumorigenesis. Cell 61:759–67 [Google Scholar]
  80. Nadauld LD, Garcia S, Natsoulis G, Bell JM, Miotke L. 81.  et al. 2014. Metastatic tumor evolution and organoid modeling implicate TGFBR2 as a cancer driver in diffuse gastric cancer. Genome Biol. 15:428 [Google Scholar]
  81. Onuma K, Ochiai M, Orihashi K, Takahashi M, Imai T. 82.  et al. 2013. Genetic reconstitution of tumorigenesis in primary intestinal cells. PNAS 110:11127–32 [Google Scholar]
  82. Cong L, Ran FA, Cox D, Lin S, Barretto R. 83.  et al. 2013. Multiplex genome engineering using CRISPR/Cas systems. Science 339:819–23 [Google Scholar]
  83. Mali P, Esvelt KM, Church GM. 84.  2013. Cas9 as a versatile tool for engineering biology. Nat. Methods 10:957–63 [Google Scholar]
  84. Drost J, van Jaarsveld RH, Ponsioen B, Zimberlin C, van Boxtel R. 85.  et al. 2015. Sequential cancer mutations in cultured human intestinal stem cells. Nature 521:43–47 [Google Scholar]
  85. Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D. 86.  et al. 2009. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 324:1457–61 [Google Scholar]
  86. Stratton MR, Campbell PJ, Futreal PA. 87.  2009. The cancer genome. Nature 458:719–24 [Google Scholar]
  87. Pon JR, Marra MA. 88.  2015. Driver and passenger mutations in cancer. Annu. Rev. Pathol. Mech. Dis. 10:25–50 [Google Scholar]
  88. Cancer Genome Atlas Netw. 89.  2012. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487:330–37 [Google Scholar]
  89. Wang K, Yuen ST, Xu J, Lee SP, Yan HH. 90.  et al. 2014. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat. Genet. 46:573–82 [Google Scholar]
  90. Chen X, Leung SY, Yuen ST, Chu KM, Ji J. 91.  et al. 2003. Variation in gene expression patterns in human gastric cancers. Mol. Biol. Cell 14:3208–15 [Google Scholar]
  91. Watanabe K, Ueno M, Kamiya D, Nishiyama A, Matsumura M. 92.  et al. 2007. A ROCK inhibitor permits survival of dissociated human embryonic stem cells. Nat. Biotechnol. 25:681–86 [Google Scholar]
  92. Cowley GS, Weir BA, Vazquez F, Tamayo P, Scott JA. 93.  et al. 2014. Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies. Sci. Data 1:140035 [Google Scholar]
  93. Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA. 94.  et al. 2014. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343:84–87 [Google Scholar]
  94. Chen S, Sanjana NE, Zheng K, Shalem O, Lee K. 95.  et al. 2015. Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell 160:1246–60 [Google Scholar]
  95. Nowell PC. 96.  1976. The clonal evolution of tumor cell populations. Science 194:23–28 [Google Scholar]
  96. Gould SJ, Eldredge N. 97.  1993. Punctuated equilibrium comes of age. Nature 366:223–27 [Google Scholar]
  97. Sottoriva A, Kang H, Ma Z, Graham TA, Salomon MP. 98.  et al. 2015. A Big Bang model of human colorectal tumor growth. Nat. Genet. 47:209–16 [Google Scholar]
  98. Greaves M, Maley CC. 99.  2012. Clonal evolution in cancer. Nature 481:306–13 [Google Scholar]
  99. Folkman J. 100.  2006. Angiogenesis. Annu. Rev. Med. 57:1–18 [Google Scholar]
  100. Hanahan D, Coussens LM. 101.  2012. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21:309–22 [Google Scholar]
  101. Meacham CE, Morrison SJ. 102.  2013. Tumour heterogeneity and cancer cell plasticity. Nature 501:328–37 [Google Scholar]
  102. Valastyan S, Weinberg RA. 103.  2011. Tumor metastasis: molecular insights and evolving paradigms. Cell 147:275–92 [Google Scholar]
  103. Calderwood SK. 104.  2013. Tumor heterogeneity, clonal evolution, and therapy resistance: an opportunity for multitargeting therapy. Discov. Med. 15:188–94 [Google Scholar]
  104. Beerenwinkel N, Antal T, Dingli D, Traulsen A, Kinzler KW. 105.  et al. 2007. Genetic progression and the waiting time to cancer. PLOS Comput. Biol. 3:e225 [Google Scholar]
  105. Bozic I, Antal T, Ohtsuki H, Carter H, Kim D. 106.  et al. 2010. Accumulation of driver and passenger mutations during tumor progression. PNAS 107:18545–50 [Google Scholar]
  106. Maley CC, Galipeau PC, Li X, Sanchez CA, Paulson TG, Reid BJ. 107.  2004. Selectively advantageous mutations and hitchhikers in neoplasms: p16 lesions are selected in Barrett's esophagus. Cancer Res. 64:3414–27 [Google Scholar]
  107. Negrini S, Gorgoulis VG, Halazonetis TD. 108.  2010. Genomic instability—an evolving hallmark of cancer. Nat. Rev. Mol. Cell Biol. 11:220–28 [Google Scholar]
  108. Ewald AJ, Brenot A, Duong M, Chan BS, Werb Z. 109.  2008. Collective epithelial migration and cell rearrangements drive mammary branching morphogenesis. Dev. Cell 14:570–81 [Google Scholar]
  109. Nelson CM, Bissell MJ. 110.  2005. Modeling dynamic reciprocity: engineering three-dimensional culture models of breast architecture, function, and neoplastic transformation. Semin. Cancer Biol. 15:342–52 [Google Scholar]
  110. Van de Wetering M, Francies HE, Francis JM, Bounova G, Iorio F. 19.  et al. 2015. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161:933–45 [Google Scholar]
  111. Endo H, Okami J, Okuyama H, Kumagai T, Uchida J. 111.  et al. 2013. Spheroid culture of primary lung cancer cells with neuregulin 1/HER3 pathway activation. J. Thorac. Oncol. 8:131–39 [Google Scholar]
  112. Kimura M, Endo H, Inoue T, Nishino K, Uchida J. 112.  et al. 2015. Analysis of ERBB ligand-induced resistance mechanism to crizotinib by primary culture of lung adenocarcinoma with EML4-ALK fusion gene. J. Thorac. Oncol. 10:527–30 [Google Scholar]
  113. Gao D, Vela I, Sboner A, Iaquinta PJ, Karthaus WR. 113.  et al. 2014. Organoid cultures derived from patients with advanced prostate cancer. Cell 159:176–87 [Google Scholar]
  114. Kondo J, Endo H, Okuyama H, Ishikawa O, Iishi H. 114.  et al. 2011. Retaining cell-cell contact enables preparation and culture of spheroids composed of pure primary cancer cells from colorectal cancer. PNAS 108:6235–40 [Google Scholar]
  115. Gillet JP, Calcagno AM, Varma S, Marino M, Green LJ. 115.  et al. 2011. Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance. PNAS 108:18708–13 [Google Scholar]
  116. Gillet JP, Varma S, Gottesman MM. 116.  2013. The clinical relevance of cancer cell lines. J. Natl. Cancer Inst. 105:452–58 [Google Scholar]
  117. Garnett MJ, Edelman EJ, Heidorn SJ, Greenman CD, Dastur A. 117.  et al. 2012. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature 483:570–75 [Google Scholar]
  118. Domcke S, Sinha R, Levine DA, Sander C, Schultz N. 118.  2013. Evaluating cell lines as tumour models by comparison of genomic profiles. Nat. Commun. 4:2126 [Google Scholar]
  119. Sugaya M, Takenoyama M, Osaki T, Yasuda M, Nagashima A. 119.  et al. 2002. Establishment of 15 cancer cell lines from patients with lung cancer and the potential tools for immunotherapy. Chest 122:282–88 [Google Scholar]
  120. Grozinsky-Glasberg S, Shimon I, Rubinfeld H. 120.  2012. The role of cell lines in the study of neuroendocrine tumors. Neuroendocrinology 96:173–87 [Google Scholar]
  121. Tentler JJ, Tan AC, Weekes CD, Jimeno A, Leong S. 121.  et al. 2012. Patient-derived tumour xenografts as models for oncology drug development. Nat. Rev. Clin. Oncol. 9:338–50 [Google Scholar]
  122. DeRose YS, Wang G, Lin YC, Bernard PS, Buys SS. 122.  et al. 2011. Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nat. Med. 17:1514–20 [Google Scholar]
  123. Arias M, Fan H. 123.  2014. The saga of XMRV: a virus that infects human cells but is not a human virus. Emerg. Microbes Infect. 3:e25 [Google Scholar]
  124. Ranga A, Gjorevski N, Lutolf MP. 124.  2014. Drug discovery through stem cell-based organoid models. Adv. Drug Deliv. Rev. 69–70:19–28 [Google Scholar]
  125. Astashkina A, Grainger DW. 125.  2014. Critical analysis of 3-D organoid in vitro cell culture models for high-throughput drug candidate toxicity assessments. Adv. Drug Deliv. Rev. 69–70:1–18 [Google Scholar]
  126. Lutolf MP, Hubbell JA. 126.  2005. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat. Biotechnol. 23:47–55 [Google Scholar]
  127. Kalluri R, Zeisberg M. 127.  2006. Fibroblasts in cancer. Nat. Rev. Cancer 6:392–401 [Google Scholar]
  128. Becker JC, Andersen MH, Schrama D, Straten PT. 128.  2013. Immune-suppressive properties of the tumor microenvironment. Cancer Immunol. Immunother. 62:1137–48 [Google Scholar]
  129. Stetler-Stevenson WG, Aznavoorian S, Liotta LA. 129.  1993. Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu. Rev. Cell Biol. 9:541–73 [Google Scholar]
  130. Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T. 130.  et al. 2005. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121:335–48 [Google Scholar]
  131. Bhowmick NA, Neilson EG, Moses HL. 131.  2004. Stromal fibroblasts in cancer initiation and progression. Nature 432:332–37 [Google Scholar]
  132. DeNardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL. 132.  et al. 2011. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov. 1:54–67 [Google Scholar]
  133. Kuang DM, Zhao Q, Peng C, Xu J, Zhang JP. 133.  et al. 2009. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. J. Exp. Med. 206:1327–37 [Google Scholar]
  134. Yang P, Li QJ, Feng Y, Zhang Y, Markowitz GJ. 134.  et al. 2012. TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma. Cancer Cell 22:291–303 [Google Scholar]
  135. Wyckoff JB, Wang Y, Lin EY, Li JF, Goswami S. 135.  et al. 2007. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res. 67:2649–56 [Google Scholar]
  136. Junttila MR, de Sauvage FJ. 136.  2013. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 501:346–54 [Google Scholar]
  137. Faget J, Biota C, Bachelot T, Gobert M, Treilleux I. 137.  et al. 2011. Early detection of tumor cells by innate immune cells leads to Treg recruitment through CCL22 production by tumor cells. Cancer Res. 71:6143–52 [Google Scholar]
  138. Ingthorsson S, Sigurdsson V, Fridriksdottir A Jr, Jonasson JG, Kjartansson J. 138.  et al. 2010. Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture. BMC Res. Notes 3:184 [Google Scholar]
  139. Woods GM, Lowenthal RM. 139.  1987. Human T lymphocyte colonies require IL2 and are inhibited by anti-Tac. Immunol. Cell Biol. 65:Pt. 197–101 [Google Scholar]
  140. Leighton J. 140.  1954. The growth patterns of some transplantable animal tumors in sponge matrix tissue culture. J. Natl. Cancer Inst. 15:275–93 [Google Scholar]
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