The cancer stem cell theory elucidates not only the issue of tumour initiation and development, tumour’s ability to metastasise and reoccur, but also the ineffectiveness of conventional cancer therapy. This review examines stem cell properties, such as self-renewal, heterogeneity, and resistance to apoptosis. The ‘niche’ hypothesis is presented, and mechanisms of division, differentiation, self-renewal and signalling pathway regulation are explained. Epigenetic alterations and mutations of genes responsible for signal transmission may promote the formation of cancer stem cells. We also present the history of development of the cancer stem cell theory and discuss the experiments that led to the discovery and confirmation of the existence of cancer stem cells. Potential clinical applications are also considered, including therapeutic models aimed at selective elimination of cancer stem cells or induction of their proper differentiation.
cancer cancer stem cells cancer stem cell theory stem cells therapeutic model
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Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF, 2003. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100: 3983–3988.CrossRefPubMedGoogle Scholar
Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. 2006. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444: 756–760.CrossRefPubMedGoogle Scholar
Bjerkvig R, Tysnes BB, Aboody KS, Najbauer J, Terzis AJA, 2005. Opinion: the origin of the cancer stem cell: current controversies and new insights. Nat Rev Cancer 5: 899–904.CrossRefPubMedGoogle Scholar
Bonnet D, Dick JE, 1997. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoetic cell. Nat Med 3: 730–737.CrossRefPubMedGoogle Scholar
Calabrese P, Tavare S, Shibata D, 2004. Pretumor progression: clonal evolution of human stem cells populations. Am J Pathol 164: 1369–1377.PubMedGoogle Scholar
auClarke MF, Becker MW, 2006. Stem cells: the real culprits in cancer? http://www.sciam.comGoogle Scholar
Kucia M, Ratajczak MZ, 2006. Stem cells as a two edged sword — from regeneration to tumor formation. J Physiol Pharmacol 57: 5–16.Google Scholar
Kucia M, Reca R, Miekus K, Wanzeck J, Wojakowski W, Janowska-Wieczorek A, et al. 2005. Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1?CXCR4 axis. Stem Cells 23: 879–894.CrossRefPubMedGoogle Scholar
Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. 2007. Identification of pancreatic cancer stem cells. Cancer Res 67: 1030–1037.CrossRefPubMedGoogle Scholar
Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, Morrison SJ, Clarke MF, 2003. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423: 302–305.CrossRefPubMedGoogle Scholar
Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G, et al. 2006. Bone morpho-genetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 444: 761–765.CrossRefPubMedGoogle Scholar
Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, et al. 2005. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 65: 5506–5511.CrossRefPubMedGoogle Scholar
Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA, 2002. Stemness: transcriptional profiling of embryonic and adult stem cells. Science 298: 597–600.CrossRefPubMedGoogle Scholar