Skip to main content

Organoid Culture: Applications in Development and Cancer

  • Chapter
  • First Online:
Ex Vivo Engineering of the Tumor Microenvironment

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The culture of primary human tissues ex vivo has historically been laden with challenges. Following the successful establishment of multiple different carcinoma cell lines, most notably HeLa cells, which helped support viral research in the 1940s and 1950s, the difficulty of propagating normal diploid cells was recognized by multiple investigators. Despite using similar 2-dimensional (2D) culture techniques that have stood the test of time—adherent culture on petri dishes using Eagle’s Medium with balanced salt solutions, 10 % calf serum, and penicillin/streptomycin - Hayflick and Moorhead perhaps best defined the limits of studying normal human tissue in a dish in 1961. Upon mincing fetal tissue they could derive multiple human diploid fibroblast cultures, but invariably the number of subcultivations was limited below 60 passages, for which they coined the term cellular “senescence,” also commonly known as the “Hayflick Limit.”

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25:585–621

    Article  CAS  PubMed  Google Scholar 

  2. Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279(5349):349–352

    Article  CAS  PubMed  Google Scholar 

  3. Kiyono T, Foster SA, Koop JI, McDougall JK, Galloway DA, Klingelhutz AJ (1998) Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells. Nature 396(6706):84–88. doi:10.1038/23962

    Article  CAS  PubMed  Google Scholar 

  4. Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA (1999) Creation of human tumour cells with defined genetic elements. Nature 400(6743):464–468. doi:10.1038/22780

    Article  CAS  PubMed  Google Scholar 

  5. Tahara H, Yasui W, Tahara E, Fujimoto J, Ito K, Tamai K, Nakayama J, Ishikawa F, Tahara E, Ide T (1999) Immuno-histochemical detection of human telomerase catalytic component, hTERT, in human colorectal tumor and non-tumor tissue sections. Oncogene 18(8):1561–1567. doi:10.1038/sj.onc.1202458

    Article  CAS  PubMed  Google Scholar 

  6. Schepers AG, Vries R, van den Born M, van de Wetering M, Clevers H (2011) Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes. EMBO J 30(6):1104–1109. doi:10.1038/emboj.2011.26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Korinek V, Barker N, Moerer P, van Donselaar E, Huls G, Peters PJ, Clevers H (1998) Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet 19(4):379–383. doi:10.1038/1270

    Article  CAS  PubMed  Google Scholar 

  8. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449(7165):1003–1007. doi:10.1038/nature06196

    Article  CAS  PubMed  Google Scholar 

  9. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459(7244):262–265. doi:10.1038/nature07935

    Article  CAS  PubMed  Google Scholar 

  10. Watanabe K, Kamiya D, Nishiyama A, Katayama T, Nozaki S, Kawasaki H, Watanabe Y, Mizuseki K, Sasai Y (2005) Directed differentiation of telencephalic precursors from embryonic stem cells. Nat Neurosci 8(3):288–296. doi:10.1038/nn1402

    Article  CAS  PubMed  Google Scholar 

  11. Eiraku M, Watanabe K, Matsuo-Takasaki M, Kawada M, Yonemura S, Matsumura M, Wataya T, Nishiyama A, Muguruma K, Sasai Y (2008) Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell 3(5):519–532. doi:10.1016/j.stem.2008.09.002

    Article  CAS  PubMed  Google Scholar 

  12. Eiraku M, Takata N, Ishibashi H, Kawada M, Sakakura E, Okuda S, Sekiguchi K, Adachi T, Sasai Y (2011) Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472(7341):51–56. doi:10.1038/nature09941

    Article  CAS  PubMed  Google Scholar 

  13. Xinaris C, Benedetti V, Rizzo P, Abbate M, Corna D, Azzollini N, Conti S, Unbekandt M, Davies JA, Morigi M, Benigni A, Remuzzi G (2012) In vivo maturation of functional renal organoids formed from embryonic cell suspensions. J Am Soc Nephrol 23(11):1857–1868. doi:10.1681/ASN.2012050505

    Article  PubMed  PubMed Central  Google Scholar 

  14. Zimmermann B (1987) Lung organoid culture. Differentiation 36(1):86–109

    Article  CAS  PubMed  Google Scholar 

  15. Levy E, Delvin E, Menard D, Beaulieu JF (2009) Functional development of human fetal gastrointestinal tract. Methods Mol Biol 550:205–224. doi:10.1007/978-1-60327-009-0_13

    Article  CAS  PubMed  Google Scholar 

  16. Nakano T, Ando S, Takata N, Kawada M, Muguruma K, Sekiguchi K, Saito K, Yonemura S, Eiraku M, Sasai Y (2012) Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell 10(6):771–785. doi:10.1016/j.stem.2012.05.009

    Article  CAS  PubMed  Google Scholar 

  17. Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA (2013) Cerebral organoids model human brain development and microcephaly. Nature 501(7467):373–379. doi:10.1038/nature12517

    Article  CAS  PubMed  Google Scholar 

  18. Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, Zheng X, Ichinose S, Nagaishi T, Okamoto R, Tsuchiya K, Clevers H, Watanabe M (2012) Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5(+) stem cell. Nat Med 18(4):618–623. doi:10.1038/nm.2695

    Article  CAS  PubMed  Google Scholar 

  19. Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, Barker N, Shroyer NF, van de Wetering M, Clevers H (2011) Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469(7330):415–418. doi:10.1038/nature09637

    Article  CAS  PubMed  Google Scholar 

  20. Sato T, Stange DE, Ferrante M, Vries RG, Van Es JH, Van den Brink S, Van Houdt WJ, Pronk A, Van Gorp J, Siersema PD, Clevers H (2011) Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology 141(5):1762–1772. doi:10.1053/j.gastro.2011.07.050

    Article  CAS  PubMed  Google Scholar 

  21. Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE, Tolle K, Hoskins EE, Kalinichenko VV, Wells SI, Zorn AM, Shroyer NF, Wells JM (2011) Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470(7332):105–109. doi:10.1038/nature09691

    Article  PubMed  Google Scholar 

  22. Watson CL, Mahe MM, Munera J, Howell JC, Sundaram N, Poling HM, Schweitzer JI, Vallance JE, Mayhew CN, Sun Y, Grabowski G, Finkbeiner SR, Spence JR, Shroyer NF, Wells JM, Helmrath MA (2014) An in vivo model of human small intestine using pluripotent stem cells. Nat Med 20(11):1310–1314. doi:10.1038/nm.3737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. McCracken KW, Cata EM, Crawford CM, Sinagoga KL, Schumacher M, Rockich BE, Tsai YH, Mayhew CN, Spence JR, Zavros Y, Wells JM (2014) Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature 516(7531):400–404. doi:10.1038/nature13863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Weiss P, Taylor AC (1960) Reconstitution of complete organs from single-cell suspensions of chick embryos in advanced stages of differentiation. Proc Natl Acad Sci U S A 46(9):1177–1185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Huch M, Dorrell C, Boj SF, van Es JH, Li VS, van de Wetering M, Sato T, Hamer K, Sasaki N, Finegold MJ, Haft A, Vries RG, Grompe M, Clevers H (2013) In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 494(7436):247–250. doi:10.1038/nature11826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Huch M, Gehart H, van Boxtel R, Hamer K, Blokzijl F, Verstegen MM, Ellis E, van Wenum M, Fuchs SA, de Ligt J, van de Wetering M, Sasaki N, Boers SJ, Kemperman H, de Jonge J, Ijzermans JN, Nieuwenhuis EE, Hoekstra R, Strom S, Vries RR, van der Laan LJ, Cuppen E, Clevers H (2015) Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160(1–2):299–312. doi:10.1016/j.cell.2014.11.050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, Zhang RR, Ueno Y, Zheng YW, Koike N, Aoyama S, Adachi Y, Taniguchi H (2013) Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499(7459):481–484. doi:10.1038/nature12271

    Article  CAS  PubMed  Google Scholar 

  28. Auerbach R, Grobstein C (1958) Inductive interaction of embryonic tissues after dissociation and reaggregation. Exp Cell Res 15(2):384–397

    Article  CAS  PubMed  Google Scholar 

  29. Xia Y, Nivet E, Sancho-Martinez I, Gallegos T, Suzuki K, Okamura D, Wu MZ, Dubova I, Esteban CR, Montserrat N, Campistol JM, Izpisua Belmonte JC (2013) Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells. Nat Cell Biol 15(12):1507–1515. doi:10.1038/ncb2872

    Article  CAS  PubMed  Google Scholar 

  30. Taguchi A, Kaku Y, Ohmori T, Sharmin S, Ogawa M, Sasaki H, Nishinakamura R (2014) Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells. Cell Stem Cell 14(1):53–67. doi:10.1016/j.stem.2013.11.010

    Article  CAS  PubMed  Google Scholar 

  31. Takasato M, Er PX, Becroft M, Vanslambrouck JM, Stanley EG, Elefanty AG, Little MH (2014) Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney. Nat Cell Biol 16(1):118–126. doi:10.1038/ncb2894

    Article  CAS  PubMed  Google Scholar 

  32. Ishii K (1966) Reconstruction of dissociated chick brain cells in rotation-mediated culture. Cytologia (Tokyo) 31(1):89–98

    Article  CAS  Google Scholar 

  33. Conti L, Cattaneo E (2010) Neural stem cell systems: physiological players or in vitro entities? Nat Rev Neurosci 11(3):176–187. doi:10.1038/nrn2761

    CAS  PubMed  Google Scholar 

  34. Kadoshima T, Sakaguchi H, Nakano T, Soen M, Ando S, Eiraku M, Sasai Y (2013) Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex. Proc Natl Acad Sci U S A 110(50):20284–20289. doi:10.1073/pnas.1315710110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Danjo T, Eiraku M, Muguruma K, Watanabe K, Kawada M, Yanagawa Y, Rubenstein JL, Sasai Y (2011) Subregional specification of embryonic stem cell-derived ventral telencephalic tissues by timed and combinatory treatment with extrinsic signals. J Neurosci 31(5):1919–1933. doi:10.1523/JNEUROSCI.5128-10.2011

    Article  CAS  PubMed  Google Scholar 

  36. Su HL, Muguruma K, Matsuo-Takasaki M, Kengaku M, Watanabe K, Sasai Y (2006) Generation of cerebellar neuron precursors from embryonic stem cells. Dev Biol 290(2):287–296. doi:10.1016/j.ydbio.2005.11.010

    Article  CAS  PubMed  Google Scholar 

  37. Layer PG, Robitzki A, Rothermel A, Willbold E (2002) Of layers and spheres: the reaggregate approach in tissue engineering. Trends Neurosci 25(3):131–134

    Article  CAS  PubMed  Google Scholar 

  38. Bertotti A, Migliardi G, Galimi F, Sassi F, Torti D, Isella C, Cora D, Di Nicolantonio F, Buscarino M, Petti C, Ribero D, Russolillo N, Muratore A, Massucco P, Pisacane A, Molinaro L, Valtorta E, Sartore-Bianchi A, Risio M, Capussotti L, Gambacorta M, Siena S, Medico E, Sapino A, Marsoni S, Comoglio PM, Bardelli A, Trusolino L (2011) A molecularly annotated platform of patient-derived xenografts (“xenopatients”) identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov 1(6):508–523. doi:10.1158/2159-8290.CD-11-0109

    Article  CAS  PubMed  Google Scholar 

  39. Gao H, Korn JM, Ferretti S, Monahan JE, Wang Y, Singh M, Zhang C, Schnell C, Yang G, Zhang Y, Balbin OA, Barbe S, Cai H, Casey F, Chatterjee S, Chiang DY, Chuai S, Cogan SM, Collins SD, Dammassa E, Ebel N, Embry M, Green J, Kauffmann A, Kowal C, Leary RJ, Lehar J, Liang Y, Loo A, Lorenzana E, Robert McDonald E 3rd, McLaughlin ME, Merkin J, Meyer R, Naylor TL, Patawaran M, Reddy A, Roelli C, Ruddy DA, Salangsang F, Santacroce F, Singh AP, Tang Y, Tinetto W, Tobler S, Velazquez R, Venkatesan K, Von Arx F, Wang HQ, Wang Z, Wiesmann M, Wyss D, Xu F, Bitter H, Atadja P, Lees E, Hofmann F, Li E, Keen N, Cozens R, Jensen MR, Pryer NK, Williams JA, Sellers WR (2015) High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response. Nat Med 21(11):1318–1325. doi:10.1038/nm.3954

    Article  CAS  PubMed  Google Scholar 

  40. Gao D, Vela I, Sboner A, Iaquinta PJ, Karthaus WR, Gopalan A, Dowling C, Wanjala JN, Undvall EA, Arora VK, Wongvipat J, Kossai M, Ramazanoglu S, Barboza LP, Di W, Cao Z, Zhang QF, Sirota I, Ran L, MacDonald TY, Beltran H, Mosquera JM, Touijer KA, Scardino PT, Laudone VP, Curtis KR, Rathkopf DE, Morris MJ, Danila DC, Slovin SF, Solomon SB, Eastham JA, Chi P, Carver B, Rubin MA, Scher HI, Clevers H, Sawyers CL, Chen Y (2014) Organoid cultures derived from patients with advanced prostate cancer. Cell 159(1):176–187. doi:10.1016/j.cell.2014.08.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Weeber F, van de Wetering M, Hoogstraat M, Dijkstra KK, Krijgsman O, Kuilman T, Gadellaa-van Hooijdonk CG, van der Velden DL, Peeper DS, Cuppen EP, Vries RG, Clevers H, Voest EE (2015) Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases. Proc Natl Acad Sci U S A 112(43):13308–13311. doi:10.1073/pnas.1516689112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. van de Wetering M, Francies HE, Francis JM, Bounova G, Iorio F, Pronk A, van Houdt W, van Gorp J, Taylor-Weiner A, Kester L, McLaren-Douglas A, Blokker J, Jaksani S, Bartfeld S, Volckman R, van Sluis P, Li VS, Seepo S, Sekhar Pedamallu C, Cibulskis K, Carter SL, McKenna A, Lawrence MS, Lichtenstein L, Stewart C, Koster J, Versteeg R, van Oudenaarden A, Saez-Rodriguez J, Vries RG, Getz G, Wessels L, Stratton MR, McDermott U, Meyerson M, Garnett MJ, Clevers H (2015) Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161(4):933–945. doi:10.1016/j.cell.2015.03.053

    Article  PubMed  Google Scholar 

  43. Boj SF, Hwang CI, Baker LA, Chio II, Engle DD, Corbo V, Jager M, Ponz-Sarvise M, Tiriac H, Spector MS, Gracanin A, Oni T, Yu KH, van Boxtel R, Huch M, Rivera KD, Wilson JP, Feigin ME, Ohlund D, Handly-Santana A, Ardito-Abraham CM, Ludwig M, Elyada E, Alagesan B, Biffi G, Yordanov GN, Delcuze B, Creighton B, Wright K, Park Y, Morsink FH, Molenaar IQ, Borel Rinkes IH, Cuppen E, Hao Y, Jin Y, Nijman IJ, Iacobuzio-Donahue C, Leach SD, Pappin DJ, Hammell M, Klimstra DS, Basturk O, Hruban RH, Offerhaus GJ, Vries RG, Clevers H, Tuveson DA (2015) Organoid models of human and mouse ductal pancreatic cancer. Cell 160(1–2):324–338. doi:10.1016/j.cell.2014.12.021

    Article  CAS  PubMed  Google Scholar 

  44. Matano M, Date S, Shimokawa M, Takano A, Fujii M, Ohta Y, Watanabe T, Kanai T, Sato T (2015) Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat Med 21(3):256–262. doi:10.1038/nm.3802

    CAS  PubMed  Google Scholar 

  45. Drost J, van Jaarsveld RH, Ponsioen B, Zimberlin C, van Boxtel R, Buijs A, Sachs N, Overmeer RM, Offerhaus GJ, Begthel H, Korving J, van de Wetering M, Schwank G, Logtenberg M, Cuppen E, Snippert HJ, Medema JP, Kops GJ, Clevers H (2015) Sequential cancer mutations in cultured human intestinal stem cells. Nature 521(7550):43–47. doi:10.1038/nature14415

    Article  CAS  PubMed  Google Scholar 

  46. Li X, Nadauld L, Ootani A, Corney DC, Pai RK, Gevaert O, Cantrell MA, Rack PG, Neal JT, Chan CW, Yeung T, Gong X, Yuan J, Wilhelmy J, Robine S, Attardi LD, Plevritis SK, Hung KE, Chen CZ, Ji HP, Kuo CJ (2014) Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture. Nat Med 20(7):769–777. doi:10.1038/nm.3585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lu H, Clauser KR, Tam WL, Frose J, Ye X, Eaton EN, Reinhardt F, Donnenberg VS, Bhargava R, Carr SA, Weinberg RA (2014) A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages. Nat Cell Biol 16(11):1105–1117. doi:10.1038/ncb3041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R, Carey VJ, Richardson AL, Weinberg RA (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121(3):335–348. doi:10.1016/j.cell.2005.02.034

    Article  CAS  PubMed  Google Scholar 

  49. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449(7162):557–563. doi:10.1038/nature06188

    Article  CAS  PubMed  Google Scholar 

  50. Malanchi I, Santamaria-Martinez A, Susanto E, Peng H, Lehr HA, Delaloye JF, Huelsken J (2012) Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 481(7379):85–89. doi:10.1038/nature10694

    Article  CAS  Google Scholar 

  51. Hanahan D, Coussens LM (2012) Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21(3):309–322. doi:10.1016/j.ccr.2012.02.022

    Article  CAS  PubMed  Google Scholar 

  52. Meads MB, Gatenby RA, Dalton WS (2009) Environment-mediated drug resistance: a major contributor to minimal residual disease. Nat Rev Cancer 9(9):665–674. doi:10.1038/nrc2714

    Article  CAS  PubMed  Google Scholar 

  53. Nakasone ES, Askautrud HA, Kees T, Park JH, Plaks V, Ewald AJ, Fein M, Rasch MG, Tan YX, Qiu J, Park J, Sinha P, Bissell MJ, Frengen E, Werb Z, Egeblad M (2012) Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance. Cancer Cell 21(4):488–503. doi:10.1016/j.ccr.2012.02.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Aref AR, Huang RY, Yu W, Chua KN, Sun W, Tu TY, Bai J, Sim WJ, Zervantonakis IK, Thiery JP, Kamm RD (2013) Screening therapeutic EMT blocking agents in a three-dimensional microenvironment. Integr Biol (Camb) 5(2):381–389. doi:10.1039/c2ib20209c

    Article  CAS  Google Scholar 

  55. Zhu Z, Aref AR, Cohoon TJ, Barbie TU, Imamura Y, Yang S, Moody SE, Shen RR, Schinzel AC, Thai TC, Reibel JB, Tamayo P, Godfrey JT, Qian ZR, Page AN, Maciag K, Chan EM, Silkworth W, Labowsky MT, Rozhansky L, Mesirov JP, Gillanders WE, Ogino S, Hacohen N, Gaudet S, Eck MJ, Engelman JA, Corcoran RB, Wong KK, Hahn WC, Barbie DA (2014) Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit. Cancer Discov 4(4):452–465. doi:10.1158/2159-8290.CD-13-0646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Barbie TU, Alexe G, Aref AR, Li S, Zhu Z, Zhang X, Imamura Y, Thai TC, Huang Y, Bowden M, Herndon J, Cohoon TJ, Fleming T, Tamayo P, Mesirov JP, Ogino S, Wong KK, Ellis MJ, Hahn WC, Barbie DA, Gillanders WE (2014) Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth. J Clin Invest 124(12):5411–5423. doi:10.1172/JCI75661

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David A. Barbie .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Cañadas, I., Barbie, D.A. (2017). Organoid Culture: Applications in Development and Cancer. In: Aref, A., Barbie, D. (eds) Ex Vivo Engineering of the Tumor Microenvironment. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-45397-2_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-45397-2_3

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-45395-8

  • Online ISBN: 978-3-319-45397-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics