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Cancer Stem Cells in Colorectal Cancer

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Stem Cells and Cancer

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Abstract

Colorectal cancer is the second most common cause of cancer death in the Western world. Due to the high prevalence of colorectal cancer and precancerous lesions, many colonoscopies, and the resulting wide availability of tissue samples, extensive knowledge is available on the stepwise process that leads to colorectal cancer. Most colorectal cancers develop from slowly growing non-invasive adenomas that take many years to grow from a single mutant crypt to an adenoma that can reach several centimeters in size before acquiring invasive characteristics. In this chapter we will discuss some of the early histopathological events in the development of colorectal cancer and try to reconcile these data with the concept of the tumor-initiating or cancer stem cell. We will show that there are many similarities between the mechanism of stem cell expansion during intestinal growth and repair and deregulated clonal expansion of stem cells in an adenoma. We argue that it is important to realize the fact that most known genetic alterations in colorectal cancer development are involved in adenoma formation and are therefore involved in clonal growth and not invasiveness. It would therefore be helpful to distinguish adenoma stem cells from carcinoma stem cells. We will then discuss the available data on the isolation and behavior of colorectal cancer stem cells.

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References

  • Agrawal, D., Chen, T., Irby, R., Quackenbush, J., Chambers, A.F., Szabo, M., Cantor, A., Coppola, D., and Yeatman, T.J. (2003). Osteopontin identified as colon cancer tumor progression marker. C. R. Biol. 326, 1041–1043.

    Article  PubMed  CAS  Google Scholar 

  • Al Hajj, M., Wicha, M.S., Benito-Hernandez, A., Morrison, S.J., and Clarke, M.F. (2003). Prospective identification of tumorigenic breast cancer cells. Proc. Natl Acad. Sci. USA 100, 3983–3988.

    Article  PubMed  CAS  Google Scholar 

  • Al Hajj, M., Becker, M.W., Wicha, M., Weissman, I., and Clarke, M.F. (2004). Therapeutic implications of cancer stem cells. Curr. Opin. Genet. Dev. 14, 43–47.

    Article  PubMed  CAS  Google Scholar 

  • Baker, S.J., Fearon, E.R., Nigro, J.M., Hamilton, S.R., Preisinger, A.C., Jessup, J.M., vanTuinen, P., Ledbetter, D.H., Barker, D.F., Nakamura, Y., White, R., and Vogelstein, B. (1989). Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244, 217–221.

    Article  PubMed  CAS  Google Scholar 

  • Barker, N., van Es, J.H., Kuipers, J., Kujala, P., van den, B.M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P.J., and Clevers, H. (2007). Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449, 1003–1007.

    Google Scholar 

  • Bhatia, M. (2001). AC133 expression in human stem cells. Leukemia 15, 1685–1688.

    PubMed  CAS  Google Scholar 

  • Bijlsma, M.F., Spek, C.A., Zivkovic, D., van de, W.S., Rezaee, F., and Peppelenbosch, M.P. (2006). Repression of smoothened by patched-dependent (pro-)vitamin D3 secretion. PLoS Biol. 4, e232.

    Article  PubMed  Google Scholar 

  • Blau, H.M., Brazelton, T.R., and Weimann, J.M. (2001). The evolving concept of a stem cell: entity or function? Cell 105, 829–841.

    Article  PubMed  CAS  Google Scholar 

  • Boman, B.M., Walters, R., Fields, J.Z., Kovatich, A.J., Zhang, T., Isenberg, G.A., Goldstein, S.D., and Palazzo, J.P. (2004). Colonic crypt changes during adenoma development in familial adenomatous polyposis: immunohistochemical evidence for expansion of the crypt base cell population. Am. J. Pathol. 165, 1489–1498.

    Article  PubMed  Google Scholar 

  • Bonnet, D. and Dick, J.E. (1997). Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. 3, 730–737.

    Article  PubMed  CAS  Google Scholar 

  • Brabletz, T., Jung, A., Spaderna, S., Hlubek, F., and Kirchner, T. (2005). Opinion: migrating cancer stem cells – an integrated concept of malignant tumour progression. Nat. Rev. Cancer 5, 744–749.

    Article  PubMed  CAS  Google Scholar 

  • Brosens, L.A., van Hattem, A., Hylind, L.M., Iacobuzio-Donahue, C., Romans, K.E., Axilbund, J., Cruz-Correa, M., Tersmette, A.C., Offerhaus, G.J., and Giardiello, F.M. (2007). Risk of colorectal cancer in juvenile polyposis. Gut 56, 965–967.

    Article  PubMed  Google Scholar 

  • Cairns, J. (2006). Cancer and the immortal strand hypothesis. Genetics 174, 1069–1072.

    Article  PubMed  CAS  Google Scholar 

  • Cardoso, J., Boer, J., Morreau, H., and Fodde, R. (2007). Expression and genomic profiling of colorectal cancer. Biochim. Biophys. Acta 1775, 103–137.

    CAS  Google Scholar 

  • Chang, Y.S., di Tomaso, E., McDonald, D.M., Jones, R., Jain, R.K., and Munn, L.L. (2000). Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc. Natl Acad. Sci. USA 97, 14608–14613.

    Article  PubMed  CAS  Google Scholar 

  • Clarke, M.F., Dick, J.E., Dirks, P.B., Eaves, C.J., Jamieson, C.H., Jones, D.L., Visvader, J., Weissman, I.L., and Wahl, G.M. (2006). Cancer stem cells–perspectives on current status and future directions: AACR Workshop on Cancer Stem Cells. Cancer Res. 66, 9339–9344.

    Article  PubMed  CAS  Google Scholar 

  • Clevers, H. (2006). Wnt/beta-catenin signaling in development and disease. Cell 127, 469–480.

    Article  PubMed  CAS  Google Scholar 

  • Dalerba, P., Dylla, S.J., Park, I.K., Liu, R., Wang, X., Cho, R.W., Hoey, T., Gurney, A., Huang, E.H., Simeone, D.M., Shelton, A.A., Parmiani, G., Castelli, C., and Clarke, M.F. (2007). Phenotypic characterization of human colorectal cancer stem cells. Proc. Natl Acad. Sci. USA 104, 10158–10163.

    Article  PubMed  CAS  Google Scholar 

  • Dean, M., Fojo, T., and Bates, S. (2005). Tumour stem cells and drug resistance. Nat. Rev. Cancer 5, 275–284.

    Article  PubMed  CAS  Google Scholar 

  • Dunker, N., Schmitt, K., Schuster, N., and Krieglstein, K. (2002). The role of transforming growth factor beta-2, beta-3 in mediating apoptosis in the murine intestinal mucosa. Gastroenterology 122, 1364–1375.

    Article  PubMed  CAS  Google Scholar 

  • Engle, S.J., Hoying, J.B., Boivin, G.P., Ormsby, I., Gartside, P.S., and Doetschman, T. (1999). Transforming growth factor beta1 suppresses nonmetastatic colon cancer at an early stage of tumorigenesis. Cancer Res. 59, 3379–3386.

    PubMed  CAS  Google Scholar 

  • Fearon, E.R. and Vogelstein, B. (1990). A genetic model for colorectal tumorigenesis. Cell 61, 759–767.

    Article  PubMed  CAS  Google Scholar 

  • Fodde, R. and Brabletz, T. (2007). Wnt/beta-catenin signaling in cancer stemness and malignant behavior. Curr. Opin. Cell Biol. 19, 150–158.

    CAS  Google Scholar 

  • Fodde, R., Smits, R., and Clevers, H. (2001). APC, signal transduction and genetic instability in colorectal cancer. Nat. Rev. Cancer 1, 55–67.

    Article  PubMed  CAS  Google Scholar 

  • Fre, S., Huyghe, M., Mourikis, P., Robine, S., Louvard, D., and Artavanis-Tsakonas, S. (2005). Notch signals control the fate of immature progenitor cells in the intestine. Nature 435, 964–968.

    Article  PubMed  CAS  Google Scholar 

  • Giardiello, F.M., Welsh, S.B., Hamilton, S.R., Offerhaus, G.J., Gittelsohn, A.M., Booker, S.V., Krush, A.J., Yardley, J.H., and Luk, G.D. (1987). Increased risk of cancer in the Peutz-Jeghers syndrome. N. Engl. J. Med. 316, 1511–1514.

    Article  PubMed  CAS  Google Scholar 

  • Greaves, L.C., Preston, S.L., Tadrous, P.J., Taylor, R.W., Barron, M.J., Oukrif, D., Leedham, S.J., Deheragoda, M., Sasieni, P., Novelli, M.R., Jankowski, J.A., Turnbull, D.M., Wright, N.A., and McDonald, S.A. (2006). Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission. Proc. Natl Acad. Sci. USA 103, 714–719.

    Article  PubMed  CAS  Google Scholar 

  • Gregorieff, A., Pinto, D., Begthel, H., Destree, O., Kielman, M., and Clevers, H. (2005). Expression pattern of Wnt signaling components in the adult intestine. Gastroenterology 129, 626–638.

    PubMed  CAS  Google Scholar 

  • Harada, N., Mizoi, T., Kinouchi, M., Hoshi, K., Ishii, S., Shiiba, K., Sasaki, I., and Matsuno, S. (2001). Introduction of antisense CD44S CDNA down-regulates expression of overall CD44 isoforms and inhibits tumor growth and metastasis in highly metastatic colon carcinoma cells. Int. J. Cancer 91, 67–75.

    Article  PubMed  CAS  Google Scholar 

  • Hardwick, J.C., van den Brink, G.R., Bleuming, S.A., Ballester, I., Van Den Brande, J.M., Keller, J.J., Offerhaus, G.J., Van Deventer, S.J., and Peppelenbosch, M.P. (2004). Bone morphogenetic protein 2 is expressed by, and acts upon, mature epithelial cells in the colon. Gastroenterology 126, 111–121.

    Article  PubMed  CAS  Google Scholar 

  • He, X.C., Zhang, J., Tong, W.G., Tawfik, O., Ross, J., Scoville, D.H., Tian, Q., Zeng, X., He, X., Wiedemann, L.M., Mishina, Y., and Li, L. (2004). BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat. Genet. 36, 1117–1121.

    Article  PubMed  CAS  Google Scholar 

  • Hemminki, A., Markie, D., Tomlinson, I., Avizienyte, E., Roth, S., Loukola, A., Bignell, G., Warren, W., Aminoff, M., Hoglund, P., Jarvinen, H., Kristo, P., Pelin, K., Ridanpaa, M., Salovaara, R., Toro, T., Bodmer, W., Olschwang, S., Olsen, A.S., Stratton, M.R., de la Chapelle, A., and Aaltonen, L.A. (1998). A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 391, 184–187.

    Article  PubMed  CAS  Google Scholar 

  • Hill, R.P. (2006). Identifying cancer stem cells in solid tumors: case not proven. Cancer Res. 66, 1891–1895.

    Article  PubMed  CAS  Google Scholar 

  • Howe, J.R., Roth, S., Ringold, J.C., Summers, R.W., Jarvinen, H.J., Sistonen, P., Tomlinson, I.P., Houlston, R.S., Bevan, S., Mitros, F.A., Stone, E.M., and Aaltonen, L.A. (1998). Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 280, 1086–1088.

    Article  PubMed  CAS  Google Scholar 

  • Howe, J.R., Bair, J.L., Sayed, M.G., Anderson, M.E., Mitros, F.A., Petersen, G.M., Velculescu, V.E., Traverso, G., and Vogelstein, B. (2001). Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat. Genet. 28, 184–187.

    Article  PubMed  CAS  Google Scholar 

  • Huff, C.A., Matsui, W., Smith, B.D., and Jones, R.J. (2006). The paradox of response and survival in cancer therapeutics. Blood 107, 431–434.

    Article  PubMed  CAS  Google Scholar 

  • Ireland, H., Kemp, R., Houghton, C., Howard, L., Clarke, A.R., Sansom, O.J., and Winton, D.J. (2004). Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin. Gastroenterology 126, 1236–1246.

    Article  PubMed  CAS  Google Scholar 

  • Jordan, C.T., Guzman, M.L., and Noble, M. (2006). Cancer stem cells. N. Engl. J. Med. 355, 1253–1261.

    Article  PubMed  CAS  Google Scholar 

  • Kiel, M.J., He, S., Ashkenazi, R., Gentry, S.N., Teta, M., Kushner, J.A., Jackson, T.L., and Morrison, S.J. (2007). Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. Nature 449, 238–242.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Kosinski, C., Li, V.S., Chan, A.S., Zhang, J., Ho, C., Tsui, W.Y., Chan, T.L., Mifflin, R.C., Powell, D.W., Yuen, S.T., Leung, S.Y., and Chen, X. (2007). Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proc. Natl Acad. Sci. USA 104, 15418–15423.

    Article  PubMed  CAS  Google Scholar 

  • Krause, D.S., Lazarides, K., von Andrian, U.H., and Van Etten, R.A. (2006). Requirement for CD44 in homing and engraftment of BCR-ABL-expressing leukemic stem cells. Nat. Med. 12, 1175–1180.

    Article  PubMed  CAS  Google Scholar 

  • Kuhnert, F., Davis, C.R., Wang, H.T., Chu, P., Lee, M., Yuan, J., Nusse, R., and Kuo, C.J. (2004). Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1. Proc. Natl Acad. Sci. USA 101, 266–271.

    Article  PubMed  CAS  Google Scholar 

  • Lapidot, T., Sirard, C., Vormoor, J., Murdoch, B., Hoang, T., Caceres-Cortes, J., Minden, M., Paterson, B., Caligiuri, M.A., and Dick, J.E. (1994). A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367, 645–648.

    Article  PubMed  CAS  Google Scholar 

  • Lee, J., Kotliarova, S., Kotliarov, Y., Li, A., Su, Q., Donin, N.M., Pastorino, S., Purow, B.W., Christopher, N., Zhang, W., Park, J.K., and Fine, H.A. (2006). Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell 9, 391–403.

    Article  PubMed  CAS  Google Scholar 

  • Leedham, S.J. and Wright, N.A. (2008). Expansion of a mutated clone: from stem cell to tumour. J. Clin. Pathol. 61, 164–171.

    Article  PubMed  CAS  Google Scholar 

  • Li, X., Madison, B.B., Zacharias, W., Kolterud, A., States, D., and Gumucio, D.L. (2007). Deconvoluting the intestine: molecular evidence for a major role of the mesenchyme in the modulation of signaling cross talk. Physiol. Genom. 29, 290–301.

    Article  CAS  Google Scholar 

  • Liaw, D., Marsh, D.J., Li, J., Dahia, P.L., Wang, S.I., Zheng, Z., Bose, S., Call, K.M., Tsou, H.C., Peacocke, M., Eng, C., and Parsons, R. (1997). Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat. Genet. 16, 64–67.

    Article  PubMed  CAS  Google Scholar 

  • Mathers, C. and Boschi-Pinto, C. (2006). Global burden of cancer in the year 2000: version 1 estimates. Report, World Health Organization, Geneva.

    Google Scholar 

  • Maw, M.A., Corbeil, D., Koch, J., Hellwig, A., Wilson-Wheeler, J.C., Bridges, R.J., Kumaramanickavel, G., John, S., Nancarrow, D., Roper, K., Weigmann, A., Huttner, W.B., and Denton, M.J. (2000). A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration. Hum. Mol. Genet. 9, 27–34.

    Article  PubMed  CAS  Google Scholar 

  • Mizrak, D., Brittan, M., and Alison, M.R. (2008). CD133: molecule of the moment. J. Pathol. 214, 3–9.

    Article  PubMed  CAS  Google Scholar 

  • Muncan, V., Sansom, O.J., Tertoolen, L., Phesse, T.J., Begthel, H., Sancho, E., Cole, A.M., Gregorieff, A., de Alboran, I., Clevers, H., and Clarke, A.R. (2006). Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc. Mol. Cell Biol. 26, 8418–8426.

    Article  PubMed  CAS  Google Scholar 

  • Nakamura, S. and Kino, I. (1984). Morphogenesis of minute adenomas in familial polyposis coli. J. Natl Cancer Inst. 73, 41–49.

    PubMed  CAS  Google Scholar 

  • Novelli, M.R., Williamson, J.A., Tomlinson, I.P., Elia, G., Hodgson, S.V., Talbot, I.C., Bodmer, W.F., and Wright, N.A. (1996). Polyclonal origin of colonic adenomas in an XO/XY patient with FAP. Science 272, 1187–1190.

    Article  PubMed  CAS  Google Scholar 

  • O'Brien, C.A., Pollett, A., Gallinger, S., and Dick, J.E. (2007). A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445, 106–110.

    Article  PubMed  Google Scholar 

  • Oshima, H., Oshima, M., Kobayashi, M., Tsutsumi, M., and Taketo, M.M. (1997). Morphological and molecular processes of polyp formation in Apc(delta716) knockout mice. Cancer Res. 57, 1644–1649.

    PubMed  CAS  Google Scholar 

  • Pierce, G.B., Nakane, P.K., Martinez-Hernandez, A., and Ward, J.M. (1977). Ultrastructural comparison of differentiation of stem cells of murine adenocarcinomas of colon and breast with their normal counterparts. J. Natl Cancer Inst. 58, 1329–1345.

    PubMed  CAS  Google Scholar 

  • Potten, C.S., Booth, C., and Pritchard, D.M. (1997). The intestinal epithelial stem cell: the mucosal governor. Int. J. Exp. Pathol. 78, 219–243.

    Article  PubMed  CAS  Google Scholar 

  • Potten, C.S., Booth, C., Tudor, G.L., Booth, D., Brady, G., Hurley, P., Ashton, G., Clarke, R., Sakakibara, S., and Okano, H. (2003). Identification of a putative intestinal stem cell and early lineage marker; musashi-1. Differentiation 71, 28–41.

    Article  PubMed  CAS  Google Scholar 

  • Regula, J., Rupinski, M., Kraszewska, E., Polkowski, M., Pachlewski, J., Orlowska, J., Nowacki, M.P., and Butruk, E. (2006). Colonoscopy in colorectal-cancer screening for detection of advanced neoplasia. N. Engl. J. Med. 355, 1863–1872.

    Article  PubMed  CAS  Google Scholar 

  • Ricci-Vitiani, L., Lombardi, D.G., Pilozzi, E., Biffoni, M., Todaro, M., Peschle, C., and De Maria, R. (2007). Identification and expansion of human colon-cancer-initiating cells. Nature 445, 111–115.

    Article  PubMed  CAS  Google Scholar 

  • Singh, S.K., Hawkins, C., Clarke, I.D., Squire, J.A., Bayani, J., Hide, T., Henkelman, R.M., Cusimano, M.D., and Dirks, P.B. (2004). Identification of human brain tumour initiating cells. Nature 432, 396–401.

    Article  PubMed  CAS  Google Scholar 

  • Sjoblom, T., Jones, S., Wood, L.D., Parsons, D.W., Lin, J., Barber, T.D., Mandelker, D., Leary, R.J., Ptak, J., Silliman, N., Szabo, S., Buckhaults, P., Farrell, C., Meeh, P., Markowitz, S.D., Willis, J., Dawson, D., Willson, J.K., Gazdar, A.F., Hartigan, J., Wu, L., Liu, C., Parmigiani, G., Park, B.H., Bachman, K.E., Papadopoulos, N., Vogelstein, B., Kinzler, K.W., and Velculescu, V.E. (2006). The consensus coding sequences of human breast and colorectal cancers. Science 314, 268–274.

    Article  PubMed  Google Scholar 

  • Southam, C.M. and Brunschwig, A. (1960). Quantitative studies of autotransplantation of human cancer. Cancer 14, 971–978.

    Article  Google Scholar 

  • Todaro, M., Perez Alea, M., Di Stefano, A.B., Cammareri, P., Vermeulen, L., Iovino, F., Tripodo, C., Russo, A., Gulotta, G., Medema, J.P., and Stassi, G. (2007a). Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 1, 389–402.

    Article  PubMed  CAS  Google Scholar 

  • Todaro, M., Perez, A.M., Scopelliti, A., Medema, J.P., and Stassi, G. (2007b). IL-4-mediated drug resistance in colon cancer stem cells. Cell Cycle 7, 309–313.

    Google Scholar 

  • Van de Wetering, M., Sancho, E., Verweij, C., de Lau, W., Oving, I., Hurlstone, A., van der Horn, K., Batlle, E., Coudreuse, D., Haramis, A.P., Tjon-Pon-Fong, M., Moerer, P., van den Born, M., Soete, G., Pals, S., Eilers, M., Medema, R., and Clevers, H. (2002). The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111, 241–250.

    Article  PubMed  Google Scholar 

  • van den Brink, G.R. (2007). Hedgehog signaling in development and homeostasis of the gastrointestinal tract. Physiol. Rev. 87, 1343–1375.

    Article  PubMed  Google Scholar 

  • van den Brink, G.R. and Offerhaus, G.J. (2007). The morphogenetic code and colon cancer development. Cancer Cell 11, 109–117.

    Article  PubMed  Google Scholar 

  • Van der Flier, L.G., Sabates-Bellver, J., Oving, I., Haegebarth, A., De Palo, M., Anti, M., van Gijn, M.E., Suijkerbuijk, S., Van de Wetering, M., Marra, G., and Clevers, H. (2007). The intestinal Wnt/TCF signature. Gastroenterology 132, 628–632.

    Article  PubMed  Google Scholar 

  • van Es, J.H., Jay, P., Gregorieff, A., van Gijn, M.E., Jonkheer, S., Hatzis, P., Thiele, A., van den Born, M., Begthel, H., Brabletz, T., Taketo, M.M., and Clevers, H. (2005a). Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nat. Cell Biol. 7, 381–386.

    Article  PubMed  Google Scholar 

  • van Es, J.H., van Gijn, M.E., Riccio, O., van den Born, M., Vooijs, M., Begthel, H., Cozijnsen, M., Robine, S., Winton, D.J., Radtke, F., and Clevers, H. (2005b). Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature 435, 959–963.

    Article  PubMed  Google Scholar 

  • Vermeulen, L., Sprick, M.R., Kemper, K., Stassi, G., and Medema, J.P. (2008). Cancer stem cells – old concepts, new insights. Cell Death Differ, 947–958.

    Google Scholar 

  • Wasan, H.S., Park, H.S., Liu, K.C., Mandir, N.K., Winnett, A., Sasieni, P., Bodmer, W.F., Goodlad, R.A., and Wright, N.A. (1998). APC in the regulation of intestinal crypt fission. J. Pathol. 185, 246–255.

    Article  PubMed  CAS  Google Scholar 

  • Weinberg, R.A. (2007). The Biology of Cancer. New York: Garland Science, pp. 413–416.

    Google Scholar 

  • Winton, D.J., Blount, M.A., and Ponder, B.A. (1988). A clonal marker induced by mutation in mouse intestinal epithelium. Nature 333, 463–466.

    Article  PubMed  CAS  Google Scholar 

  • Wood, L.D., Parsons, D.W., Jones, S., Lin, J., Sjoblom, T., Leary, R.J., Shen, D., Boca, S.M., Barber, T., Ptak, J., Silliman, N., Szabo, S., Dezso, Z., Ustyanksky, V., Nikolskaya, T., Nikolsky, Y., Karchin, R., Wilson, P.A., Kaminker, J.S., Zhang, Z., Croshaw, R., Willis, J., Dawson, D., Shipitsin, M., Willson, J.K., Sukumar, S., Polyak, K., Park, B.H., Pethiyagoda, C.L., Pant, P.V., Ballinger, D.G., Sparks, A.B., Hartigan, J., Smith, D.R., Suh, E., Papadopoulos, N., Buckhaults, P., Markowitz, S.D., Parmigiani, G., Kinzler, K.W., Velculescu, V.E., and Vogelstein, B. (2007). The genomic landscapes of human breast and colorectal cancers. Science 318, 1108–1113.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental Molecular Medicine (CEMM), Academic Medical Center, Amsterdam, The Netherlands

    Louis Vermeulen & Jan Paul Medema

  2. Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, The Netherlands

    James C.H. Hardwick

  3. Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, The Netherlands

    Gijs R. van den Brink

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  1. Louis Vermeulen
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  2. Jan Paul Medema
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  4. Gijs R. van den Brink
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Correspondence to Gijs R. van den Brink .

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    Vermeulen, L., Medema, J.P., Hardwick, J.C., van den Brink, G.R. (2009). Cancer Stem Cells in Colorectal Cancer. In: Majumder, S. (eds) Stem Cells and Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-89611-3_9

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