Applying the principles of stem-cell biology to cancer (original) (raw)

• Sell, S. & Pierce, G. B. Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. Lab. Invest. 70, 6–22 (1994).
  CAS PubMed Google Scholar
• Wechsler-Reya, R. & Scott, M. P. The developmental biology of brain tumors. Annu. Rev. Neurosci. 24, 385–428 (2001).
  Article CAS PubMed Google Scholar
• Fearon, E. R., Burke, P. J., Schiffer, C. A., Zehnbauer, B. A. & Vogelstein, B. Differentiation of leukemia cells to polymorphonuclear leukocytes in patients with acute nonlymphocytic leukemia. N. Engl. J. Med. 315, 15–24 (1986).
  CAS PubMed Google Scholar
• Fialkow, P. J. et al. Clonal development, stem-cell differentiation, and clinical remissions in acute nonlymphocytic leukemia. N. Engl. J. Med. 20, 468–473 (1987).
  Google Scholar
• Bonnet, D. & Dick, J. E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Med. 3, 730–737 (1997).
  CAS PubMed Google Scholar
• Reya, T., Morrison, S. J., Clarke, M. F. & Weissman, I. L. Stem cells, cancer, and cancer stem cells. Nature 414, 105–111 (2001).
  CAS PubMed Google Scholar
• Hamburger, A. W. & Salmon, S. E. Primary bioassay of human tumor stem cells. Science 197, 461–463 (1977).
  CAS PubMed Google Scholar
• Lapidot, T. et al. A cell initiating human acute myeloid leukemia after transplantation into SCID mice. Nature 17, 645–648 (1994).
  Google Scholar
• Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J. & Clarke, M. F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl Acad. Sci. USA 100, 3983–3988 (2003). Not all human breast cancer cells are equal in terms of their ability to form tumours in immunocompromised mice, and the tumorigenic subset of cells exhibits properties of cancer stem cells. The tumorigenic cell population represents a minority of cells within the tumours, but can be isolated from most of the patients studied based on a unique surface-marker expression pattern.
  CAS PubMed PubMed Central Google Scholar
• Singh, S. K. et al. Identification of a cancer stem cell in human brain tumours. Cancer Res. 63, 5821–5828 (2003). Not all human brain cancer cells are equal in terms of their ability to proliferate in culture, and the more proliferative subset of cells exhibits markers and functions of neural stem cells.
  CAS PubMed Google Scholar
• Taipale, J. & Beachy, P. A. The hedgehog and Wnt signaling pathways in cancer. Nature 411, 349–354 (2001).
  CAS PubMed Google Scholar
• Zhu, Y. & Parada, L. F. The molecular and genetic basis of neurological tumours. Nature Rev. Cancer 2, 616–626 (2002).
  CAS Google Scholar
• Park, I. K. et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423, 302–305 (2003). Haematopoietic stem-cell self-renewal in vivo is dependent on BMI1 , and BMI1 -deficient haematopoietic stem cells do not persist into adulthood.
  CAS PubMed Google Scholar
• Lessard, J. & Sauvageau, G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 423, 255–260 (2003). Proliferation of leukaemic stem cells is dependent on BMI1 , and BMI1 -deficient leukaemia cells fail to induce disease following transplantation. This shows that proliferation of leukaemic stem cells depends on a pathway that is also crucial for the self-renewal of normal haematopoietic stem cells.
  CAS PubMed Google Scholar
• Hemmati, H. D. et al. Pediatric brain tumor stem cells. Ann. Neurol. 54, S117 (2003).
  Google Scholar
• Salmon, S. E. et al. Quantitation of differential sensitivity of human-tumor stem cells to anticancer drugs. N. Engl. J. Med. 298, 1321–1327 (1978).
  CAS PubMed Google Scholar
• McCulloch, E. A. Stem cells in normal and leukemic hemopoiesis (Henry Stratton Lecture, 1982). Blood 62, 1–13 (1983).
  CAS PubMed Google Scholar
• Trott, K. R. Tumour stem cells: the biological concept and its application in cancer treatment. Radiother. Oncol. 30, 1–5 (1994).
  CAS PubMed Google Scholar
• Kummermehr, J. & Trott, K. -R. in Stem Cells (ed. Potten, C. S.) 363–399 (Academic Press, New York, 1997).
  Google Scholar
• Bruce, W. R. & Gaag, H. V. D. A quantitative assay for the number of murine lymphoma cells capable of proliferation in vivo. Nature 199, 79–80 (1963).
  CAS PubMed Google Scholar
• Wodinsky, I., Swiniarski, J. & Kensler, C. J. Spleen colony studies of leukemia L1210. I. Growth kinetics of lymphocytic L1210 cells in vivo as determined by spleen colony assay. Cancer Chemother. Rep. 51, 415–421 (1967).
  Google Scholar
• Ignatova, T. N. et al. Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia 39, 193–206 (2002).
  PubMed Google Scholar
• Knudson, A. G. Jr, Strong, L. C. & Anderson, D. E. Heredity and cancer in man. Prog. Med. Genet. 9, 113–158 (1973).
  PubMed Google Scholar
• Bhatia, M., Wang, J. C., Kapp, U., Bonnet, D. & Dick, J. E. Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc. Natl Acad. Sci. USA 94, 5320–5325 (1997).
  CAS PubMed PubMed Central Google Scholar
• Pereira, D. S. et al. Retroviral transduction of TLS-ERG initiates a leukemogenic program in normal human hematopoietic cells. Proc. Natl Acad. Sci. USA 95, 8239–8244 (1998).
  CAS PubMed PubMed Central Google Scholar
• Kelly, L. M. & Gilliland, D. G. Genetics of myeloid leukemias. Annu. Rev. Genomics Hum. Genet. 3, 179–198 (2002).
  CAS PubMed Google Scholar
• Blair, A., Hogge, D. E., Ailles, L. E., Lansdorp, P. M. & Sutherland, H. J. Lack of expression of Thy-1 (CD90) on acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo. Blood 89, 3104–3112 (1997).
  CAS PubMed Google Scholar
• Jordan, C. T. et al. The interleukin-3 receptor α chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia 14, 1777–1784 (2000).
  CAS PubMed Google Scholar
• Polakis, P. The oncogenic activation of β-catenin. Curr. Opin. Genet. Dev. 9, 15–21 (1999).
  CAS PubMed Google Scholar
• Zhu, A. J. & Watt, F. M. β-catenin signalling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion. Development 126, 2285–2298 (1999).
  CAS PubMed Google Scholar
• Willert, K. et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423, 448–452 (2003). Soluble Wnt3a can promote the self-renewal of haematopoeitic stem cells in culture.
  CAS PubMed Google Scholar
• Reya, T. et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423, 409–414 (2003). Wnt/β-catenin-pathway activation promotes the self-renewal of haematopoietic stem cells in culture.
  CAS PubMed Google Scholar
• Wechsler-Reya, R. J. & Scott, M. P. Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron 22, 103–114 (1999).
  CAS PubMed Google Scholar
• Taylor, M. D. et al. Mutations in SUFU predispose to medulloblastoma. Nature Genet. 31, 306–310 (2002).
  CAS PubMed Google Scholar
• Lai, K., Kaspar, B. K., Gage, F. H. & Schaffer, D. V. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nature Neurosci. 6, 21–27 (2003).
  CAS PubMed Google Scholar
• Wetmore, C. Sonic hedgehog in normal and neoplastic proliferation: insight gained from human tumors and animal models. Curr. Opin. Genet. Dev. 13, 34–42 (2003).
  CAS PubMed Google Scholar
• Pear, W. S. et al. Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles. J. Exp. Med. 183, 2283–2291 (1996).
  CAS PubMed Google Scholar
• Varnum-Finney, B. et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nature Med. 6, 1278–1281 (2000).
  CAS PubMed Google Scholar
• Henrique, D. et al. Maintenance of neuroepithelial progenitor cells by δ-Notch signalling in the embryonic chick retina. Curr. Biol. 7, 661–670 (1997).
  CAS PubMed Google Scholar
• Di Cristofano, A. & Pandolfi, P. P. The multiple roles of PTEN in tumor suppression. Cell 100, 387–390 (2000).
  CAS PubMed Google Scholar
• Groszer, M. et al. Negative regulation of neural stem/progenitor cell proliferation by the pten tumor suppressor gene in vivo. Science 1, 1 (2001).
  Google Scholar
• Morrison, S. J. Pten-uating neural growth. Nature Med. 8, 16–18 (2002).
  CAS PubMed Google Scholar
• Chenn, A. & Walsh, C. A. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 297, 365–369 (2002).
  CAS PubMed Google Scholar
• Zurawel, R. H., Chiappa, S. A., Allen, C. & Raffel, C. Sporadic medulloblastomas contain oncogenic β-catenin mutations. Cancer Res. 58, 896–899 (1998).
  CAS PubMed Google Scholar
• Gat, U., DasGupta, R., Degenstein, L. & Fuchs, E. De novo hair follicle morphogenesis and hair tumors in mice expressing a truncated β-catenin in skin. Cell 95, 605–614 (1998).
  CAS PubMed Google Scholar
• Chan, E. F., Gat, U., McNiff, J. M. & Fuchs, E. A common human skin tumour is caused by activating mutations in β-catenin. Nature Genet. 21, 410–413 (1999).
  CAS PubMed Google Scholar
• Korinek, V. et al. Depletion of epithelial stem cell compartments in the small intestine of mice lacking Tcf-4. Nature Genet. 19, 379–383 (1998).
  CAS PubMed Google Scholar
• Batlle, E. et al. β-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell 111, 251–263 (2002).
  CAS PubMed Google Scholar
• van de Wetering,, M. et al. The β-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111, 241–250 (2002). References 47–49 show that the Wnt/β-catenin pathway is required to maintain the stem-cell identity of normal gut epithelial stem cells as well as colorectal cancer cells, and that it promotes the proliferation of both cell types by acting through similar downstream pathways.
  CAS Google Scholar
• Powell, S. M. et al. APC mutations occur early during colorectal tumorigenesis. Nature 359, 235–237 (1992).
  CAS PubMed Google Scholar
• Moser, A. R., Dove, W. F., Roth, K. A. & Gordon, J. I. The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system. J. Cell Biol. 116, 1517–1526 (1992).
  CAS PubMed Google Scholar
• Kinzler, K. W. & Vogelstein, B. Lessons from hereditary colorectal cancer. Cell 87, 159–170 (1996).
  CAS PubMed Google Scholar
• Bienz, M. & Clevers, H. Linking colorectal cancer to Wnt signaling. Cell 103, 311–320 (2000).
  CAS PubMed Google Scholar
• Austin, T. W., Solar, G. P., Ziegler, F. C., Liem, L. & Matthews, W. A role for the Wnt gene family in hematopoiesis: expansion of multilineage progenitor cells. Blood 89, 3624–3635 (1997).
  CAS PubMed Google Scholar
• Van Den Berg, D. J., Sharma, A. K., Bruno, E. & Hoffman, R. Role of members of the Wnt gene family in human hematopoiesis. Blood 92, 3189–3202 (1998).
  CAS PubMed Google Scholar
• Murdoch, B. et al. Wnt-5A augments repopulating capacity and primitive hematopoietic development of human blood stem cells in vivo. Proc. Natl Acad. Sci. USA 100, 3422–3427 (2003).
  CAS PubMed PubMed Central Google Scholar
• Haegel, H. et al. Lack of β-catenin affects mouse development at gastrulation. Development 121, 3529–3537 (1995).
  CAS PubMed Google Scholar
• Brault, V. et al. Inactivation of the β-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development. Development 128, 1253–1264 (2001).
  CAS PubMed Google Scholar
• Yoshikawa, Y., Fujimori, T., McMahon, A. P. & Takada, S. Evidence that absence of Wnt-3a signaling promotes neuralization instead of paraxial mesoderm development in the mouse. Dev. Biol. 183, 234–242 (1997).
  CAS PubMed Google Scholar
• Chung, E. J. et al. Regulation of leukemic cell adhesion, proliferation, and survival by β-catenin. Blood 100, 982–990 (2002).
  CAS PubMed Google Scholar
• Qiang, Y. W., Endo, Y., Rubin, J. S. & Rudikoff, S. Wnt signaling in B-cell neoplasia. Oncogene 22, 1536–1545 (2003).
  CAS PubMed Google Scholar
• van Kemenade, F. J. et al. Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma. Blood 97, 3896–3901 (2001).
  CAS PubMed Google Scholar
• Visser, H. P. et al. The Polycomb group protein EZH2 is upregulated in proliferating, cultured human mantle cell lymphoma. Br. J. Haematol. 112, 950–958 (2001).
  CAS PubMed Google Scholar
• Ohta, H. et al. Polycomb group gene rae28 is required for sustaining activity of hematopoietic stem cells. J. Exp. Med. 195, 759–770 (2002).
  CAS PubMed PubMed Central Google Scholar
• Varambally, S. et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419, 624–629 (2002).
  CAS PubMed Google Scholar
• Bea, S. et al. BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas. Cancer Res. 61, 2409–2412 (2001).
  CAS PubMed Google Scholar
• Alkema, M. J., Jacobs, H., van Lohuizen, M. & Berns, A. Pertubation of B and T cell development and predisposition to lymphomagenesis in Emu Bmi1 transgenic mice require the Bmi1 RING finger. Oncogene 15, 899–910 (1997).
  CAS PubMed Google Scholar
• Haupt, Y., Bath, M. L., Harris, A. W. & Adams, J. M. bmi-1 transgene induces lymphomas and collaborates with myc in tumorigenesis. Oncogene 8, 3161–3164 (1993).
  CAS PubMed Google Scholar
• van der Lugt, N. M. et al. Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene. Genes Dev. 8, 757–769 (1994).
  CAS PubMed Google Scholar
• Jacobs, J. J., Kieboom, K., Marino, S., DePinho, R. A. & van Lohuizen, M. The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature 397, 164–168 (1999).
  CAS PubMed Google Scholar
• Jacobs, J. J. et al. Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF. Genes Dev. 13, 2678–2790 (1999).
  CAS PubMed PubMed Central Google Scholar
• Lessard, J., Baban, S. & Sauvageau, G. Stage-specific expression of polycomb group genes in human bone marrow cells. Blood 91, 1216–1224 (1998).
  CAS PubMed Google Scholar
• Jacobs, J. J. L. & Lohuizen, M. V. Polycomb repression: from cellular memory to cellular proliferation and cancer. Biochim. Biophys. Acta 1602, 151–161 (2002).
  CAS PubMed Google Scholar
• Chaudhary, P. M. & Roninson, I. B. Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. Cell 66, 85–94 (1991).
  CAS PubMed Google Scholar
• Zhou, S. et al. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nature Med. 7, 1028–1034 (2001).
  CAS PubMed Google Scholar
• Pallis, M. & Russell, N. P-glycoprotein plays a drug-efflux-independent role in augmenting cell survival in acute myeloblastic leukemia and is associated with modulation of a sphingomyelin-ceramide apoptotic pathway. Blood 95, 2897–2904 (2000).
  CAS PubMed Google Scholar
• Johnstone, R. W., Cretney, E. & Smyth, M. J. P-glycoprotein protects leukemia cells against caspase-dependent, but not caspase-independent, cell death. Blood 93, 1075–1085 (1999).
  CAS PubMed Google Scholar
• Bittner, M. et al. Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature 406, 536–540 (2000).
  CAS PubMed Google Scholar
• Perou, C. M. et al. Molecular portraits of human breast tumours. Nature 406, 747–752 (2000).
  CAS PubMed Google Scholar
• Alizadeh, A. A. et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403, 503–511 (2000).
  CAS PubMed Google Scholar
• Pomeroy, S. L. et al. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415, 436–442 (2002).
  CAS PubMed Google Scholar
• Shipp, M. A. et al. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nature Med. 8, 68–74 (2002).
  CAS PubMed Google Scholar
• Guzman, M. L. et al. Preferential induction of apoptosis for primary human leukemic stem cells. Proc. Natl Acad. Sci. USA 99, 16220–16225 (2002). Shows that it is possible to identify therapeutic agents that kill leukaemic stem cells but not normal haematopoietic stem cells.
  CAS PubMed PubMed Central Google Scholar
• Stephenson, W. T., Poirier, S. M., Rubin, L. & Einhorn, L. H. Evaluation of reproductive capacity in germ-cell tumor patients following treatment with cisplatin, etoposide, and bleomycin. J. Clin. Oncol. 13, 2278–2280 (1995).
  CAS PubMed Google Scholar
• Huelsken, J., Vogel, R., Erdmann, B., Cotsarelis, G. & Birchmeier, W. β-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105, 533–545 (2001). References 30, 45, 46 and 85 show that the WNT/ β-catenin pathway regulates the self-renewal of normal epidermal stem cells and that mutations that over-activate this pathway lead to the formation of tumours in the epidermis.
  CAS PubMed Google Scholar
• Cui, H., Meng, Y. & Bulleit, R. F. Inhibition of glycogen synthase kinase 3β activity regulates proliferation of cultured cerebellar granule cells. Brain Res. Dev. Brain Res. 111, 177–188 (1998).
  CAS PubMed Google Scholar
• St-Jacques, B. et al. Sonic hedgehog signaling is essential for hair development. Curr. Biol. 8, 1058–1068 (1998).
  CAS PubMed Google Scholar
• Chiang, C. et al. Essential role for Sonic hedgehog during hair follicle morphogenesis. Dev. Biol. 205, 1–9 (1999).
  CAS PubMed Google Scholar
• Johnson, R. L. et al. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 272, 1668–1671 (1996).
  CAS PubMed Google Scholar
• Oro, A. E. et al. Basal cell carcinomas in mice overexpressing sonic hedgehog. Science 276, 817–821 (1997).
  CAS PubMed Google Scholar
• Dahmane, N., Lee, J., Robins, P., Heller, P. & Ruiz i Altaba, A. Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours. Nature 389, 876–881 (1997).
  CAS PubMed Google Scholar
• Raffel, C. et al. Sporadic medulloblastomas contain PTCH mutations. Cancer Res. 57, 842–845 (1997).
  CAS PubMed Google Scholar
• Pietsch, T. et al. Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched. Cancer Res. 57, 2085–2088 (1997).
  CAS PubMed Google Scholar
• Goodrich, L. V., Milenkovic, L., Higgins, K. M. & Scott, M. P. Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277, 1109–1113 (1997).
  CAS PubMed Google Scholar
• Ruiz i Altaba, A., Sanchez, P. & Dahmane, N. Gli and hedgehog in cancer: tumours, embryos and stem cells. Nature Rev. Cancer 2, 361–327 (2002).
  CAS Google Scholar
• Chepko, G. & Dickson, R. B. Ultrastructure of the putative stem cell niche in rat mammary epithelium. Tissue Cell 35, 83–93 (2003).
  CAS PubMed Google Scholar
• Jhappan, C. et al. Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands. Genes Dev. 6, 345–355 (1992).
  CAS PubMed Google Scholar
• Duerr, E. M. et al. PTEN mutations in gliomas and glioneuronal tumors. Oncogene 16, 2259–2264 (1998).
  CAS PubMed Google Scholar
• Perez-Losada, J. & Balmain, A. Stem-cell hierarchy in skin cancer. Nature Rev. Cancer 3, 434–443 (2003).
  CAS Google Scholar
• Liu, C. et al. Control of β-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108, 837–847 (2002).
  CAS PubMed Google Scholar
• Lowe, S. W. & Sherr, C. J. Tumor suppression by Ink4a–Arf: progress and puzzles. Curr. Opin. Genet. Dev. 13, 77–83 (2003).
  CAS PubMed Google Scholar
• Pierce, G. B. & Speers, W. C. Tumors as caricatures of the process of tissue renewal: prospects for therapy by directing differentiation. Cancer Res. 48, 1996–2004 (1988).
  CAS PubMed Google Scholar
• Jain, M. et al. Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science 297, 102–104 (2002). Even a transient loss of MYC function can lead to an irreversible loss of neoplastic cells. This is consistent with the idea that MYC is required to maintain the state of cancer stem cells, much as it would be expected to be required for normal stem-cell self-renewal. So, targeting pathways that are required for maintenance of stem-cell identity might be used to convert malignancies into benign tumours.
  CAS PubMed Google Scholar