J Breast Cancer.  2007 Sep;10(3):173-179. 10.4048/jbc.2007.10.3.173.

Cancer Stem Cells

Affiliations
  • 1Department of Surgery, Cheil General Hospital and Women's Healthcare Center, College of Medicine, Kwandong University, Seoul, Korea. hmh1916@gmail.com
  • 2Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.

Abstract

Recent results have supported the cancer stem cells hypothesis in which tumors originate from tissue stem cells or their early progenitors and, as a result, produce tumors that retain stem cell properties. These properties include selfrenewal that drives tumorigenesis and differentiation that contributes to cellular heterogeneity. The number of these cells is very small, and is tightly controlled by the self-renewal pathway and the signals of their environment (niche). Evidence for the existence of cancer stem cells has been reported for a number of human cancers including leukemia, cancers of the breast, brain, and colon. Although our understanding of the biology of these cancer stem cells remains rudimentary, the existence of these cells has implications for current conceptualization of malignant transformation and targeted therapy for the treatment of cancer.

Keyword

Cancer stem cells; Self renewal; Targeted therapy

MeSH Terms

Biology
Brain
Breast
Carcinogenesis
Colon
Humans
Leukemia
Neoplastic Stem Cells*
Population Characteristics
Stem Cells

Figure

  • Fig 1. Detection of PERV RNA in plasma (A) and culture supernatant of PBMC (B) from SNU miniature pig by RT-PCR. (A) M, molecular marker; 1, PK-15; 2, plasma; 3, distilled water control (B) M, molecular marker; 1, PK-15; 2, culture supernatant of PK-15; 3-8, culture supernatant of PBMC treated with PMA, PHA, PMA plus PHA, LPS, PGE2, and media; 9, distilled water control.

  • Fig 2. Signaling pathways that regulate self-renewal mechanisms during normal stem cell development and during transformation. Wnt, Shh and Notch pathways have been shown to contribute to the self-renewal of stem cells and/or progenitors in a variety of organs, including the hematopoietic and nervous systems. When dysregulated, these pathways can contribute to oncogenesis. Mutations of these pathways have been associated with a number of human tumors, including colon carcinoma and epidermal tumors (Wnt), medulloblastoma and basal cell carcinoma (Shh), and T-cell leukemias (Notch). (Images courtesy of Eye of Science/SPL and R. Wechsler- Reya/M. Scott/Annual reviews.)


Reference

1. Al-Hajj M, Clarke MF. Self-renewal and solid tumor stem cells. Oncogene. 2004; 23:7274–7282.
Article
2. Cohnheim J. Congenitales, quergestreigtes muskelsarkom der nieren. Virchows Arch. 1875; 65:64. Cited from Sell S. Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol 2004;51: 1-28.
3. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997; 3:730–737.
Article
4. Wicha MS, Liu S, Dontu G. Cancer stem cells: an old idea--a paradigm shift. Cancer Res. 2006; 66:1883–1890.
Article
5. Burce WR, Van Der Gaag H. Quantitative assay for the number of murine lymphoma cells capable of proligeration in vivo. Nature. 1963; 199:79–80.
6. Kleinsmith LJ, Pierce GB. Multipotentiality of single embryonal carcinoma cells. Cancer Res. 1964; 24:1544–1551.
7. Makino S. Further evidence favoring the concept of the stem cell in ascites tumors of rats. Ann NY Acad Sci. 1956; 63:818–830.
Article
8. Park CH, Bergsagel DE, McCulloch EA. Mouse myeloma tumor stem cells: a primary cell culture assay. J Natl Cancer Inst. 1971; 46:411–422.
9. Bruce WR, Van Der Gaag H. Quantitative assay for the number of murine lymphoma cells capable of proligeration in vivo. Nature. 1963; 199:79–80.
10. Weinberg RA. The molecular basis of oncogenes and tumor suppressor genes. Ann N Y Acad Sci. 1995; 758:331–338.
Article
11. Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med. 2004; 10:789–799.
Article
12. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001; 414:105–111.
Article
13. Varnum-Finney B, Xu L, Brashem-Stein C, Nourigat C, Flowers D, Bakkour S, et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat Med. 2000; 6:1278–1281.
Article
14. Henrique D, Hirsinger E, Adam J, Le Roux I, Pourquie O, Ish-Horowicz D, et al. Maintenance of neuroepithelial progenitor cells by Delta-Notch signalling in the embryonic chick retina. Curr Biol. 1997; 7:661–670.
Article
15. Austin J, Kimble J. glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans. Cell. 1987; 51:589–599.
Article
16. Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD, et al. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell. 1991; 66:649–661.
Article
17. Bhardwaj G, Murdoch B, Wu D, Baker DP, Williams KP, Chadwick K, et al. Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat Immunol. 2001; 2:172–180.
Article
18. Wechsler-Reya RJ, Scott MP. Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron. 1999; 22:103–114.
Article
19. Zhang Y, Kalderon D. Hedgehog acts as a somatic stem cell factor in the Drosophila ovary. Nature. 2001; 410:599–604.
Article
20. Wechsler-Reya R, Scott MP. The developmental biology of brain tumors. Annu Rev Neurosci. 2001; 24:385–428.
Article
21. Gailani MR, Bale AE. Acquired and inherited basal cell carcinomas and the patched gene. Adv Dermatol. 1999; 14:261–283.
22. Zhu AJ, Watt FM. beta-catenin signalling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion. Development. 1999; 126:2285–2298.
Article
23. Korinek V, Barker N, Moerer P, van Donselaar E, Huls G, Peters PJ, et al. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet. 1998; 19:379–383.
Article
24. Polakis P. Wnt signaling and cancer. Genes Dev. 2000; 14:1837–1851.
Article
25. Chan EF, Gat U, McNiff JM, Fuchs E. A common human skin tumour is caused by activating mutations in beta-catenin. Nat Genet. 1999; 21:410–413.
26. Woodward WA, Chen MS, Behbod F, Rosen JM. On mammary stem cells. J Cell Sci. 2005; 118:3585–3594.
Article
27. Miller SJ, Lavker RM, Sun TT. Interpreting epithelial cancer biology in the context of stem cells: tumor properties and therapeutic implications. Biochim Biophys Acta. 2005; 1756:25–52.
Article
28. Crowe DL, Parsa B, Sinha UK. Relationships between stem cells and cancer stem cells. Histol Histopathol. 2004; 19:505–509.
29. Young HE, Duplaa C, Romero-Ramos M, Chesselet MF, Vourc\'h P, Yost MJ, et al. Adult reserve stem cells and their potential for tissue engineering. Cell Biochem Biophys. 2004; 40:1–80.
Article
30. Beachy PA, Karhadkar SS, Berman DM. Tissue repair and stem cell renewal in carcinogenesis. Nature. 2004; 432:324–331.
Article
31. Valk-Lingbeek ME, Bruggeman SW, van Lohuizen M. Stem cells and cancer; the polycomb connection. Cell. 2004; 118:409–418.
32. Tsai RY. A molecular view of stem cell and cancer cell self-renewal. Int J Biochem Cell Biol. 2004; 36:684–694.
Article
33. Blair A, Hogge DE, Ailles LE, Lansdorp PM, Sutherland HJ. Lack of expression of Thy-1 (CD90) on acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo. Blood. 1997; 89:3104–3112.
Article
34. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004; 432:396–401.
Article
35. Singh SK, Clarke ID, Hide T, Dirks PB. Cancer stem cells in nervous system tumors. Oncogene. 2004; 23:7267–7273.
Article
36. Kondo T, Setoguchi T, Taga T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA. 2004; 101:781–786.
Article
37. Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, et al. A distinct \"side population\" of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA. 2004; 101:14228–14233.
Article
38. Locke M, Heywood M, Fawell S, Mackenzie IC. Retention of intrinsic stem cell hierarchies in carcinoma-derived cell lines. Cancer Res. 2005; 65:8944–8950.
Article
39. Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K, Tang DG. Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2- cancer cells are similarly tumorigenic. Cancer Res. 2005; 65:6207–6219.
Article
40. Polyak K, Hahn WC. Roots and stems: stem cells in cancer. Nat Med. 2006; 12:296–300.
Article
41. Caussinus E, Gonzalez C. Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nat Genet. 2005; 37:1125–1129.
Article
42. Lininger RA, Fujii H, Man YG, Gabrielson E, Tavassoli FA. Comparison of loss heterozygosity in primary and recurrent ductal carcinoma in situ of the breast. Mod Pathol. 1998; 11:1151–1159.
43. Passegue E, Jamieson CH, Ailles LE, Weissman IL. Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics? Proc Natl Acad Sci U S A. 2003; 100(Suppl 1):11842–11849.
Article
44. Prindull G. Hypothesis: cell plasticity, linking embryonal stem cells to adult stem cell reservoirs and metastatic cancer cells? Exp Hematol. 2005; 33:738–746.
Article
45. Bates RC, Mercurio AM. The epithelial-mesenchymal transition (EMT) and colorectal cancer progression. Cancer Biol Ther. 2005; 4:365–370.
46. Kai T, Spradling A. Differentiating germ cells can revert into functional stem cells in Drosophila melanogaster ovaries. Nature. 2004; 428:564–569.
Article
47. Cozzio A, Passegue E, Ayton PM, Karsunky H, Cleary ML, Weissman IL. Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev. 2003; 17:3029–3035.
Article
48. Al-Hajj M, Becker MW, Wicha M, Weissman I, Clarke MF. Therapeutic implications of cancer stem cells. Curr Opin Genet Dev. 2004; 14:43–47.
Article
49. Brenton JD, Carey LA, Ahmed AA, Caldas C. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol. 2005; 23:7350–7360.
Article
50. Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005; 5:275–284.
Article
51. Pece S, Serresi M, Santolini E, Capra M, Hulleman E, Galimberti V, et al. Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis. J Cell Biol. 2004; 167:215–221.
Article
52. Weijzen S, Rizzo P, Braid M, Vaishnav R, Jonkheer SM, Zlobin A, et al. Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nat Med. 2002; 8:979–986.
Article
53. Karhadkar SS, Bova GS, Abdallah N, Dhara S, Gardner D, Maitra A, et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature. 2004; 431:707–712.
Article
54. Bosl GJ, Motzer RJ. Testicular germ-cell cancer. N Engl J Med. 1997; 337:242–253.
Article
55. Bhatia R, Holtz M, Niu N, Gray R, Snyder DS, Sawyers CL, et al. Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment. Blood. 2003; 101:4701–4707.
Article
56. Smalley M, Ashworth A. Stem cells and breast cancer: a field in transit. Nat Rev Cancer. 2003; 3:832–844.
Article
Full Text Links
  • JBC
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr