Cancer stem cells in solid tumors and leukemia

Abstract

Cancer stem cells (CSCs) are cells that drive tumorigenesis, as well as give rise to a large population of differentiated progeny that make up the bulk of the tumor. The same specific signaling pathways play a functional role in CSC renewal and/or differentiation as with normal stem cells, the only difference being that the same signaling pathways are dysregulated in CSCs. In addition, recent studies have demonstrated that CSCs are resistant to chemo- and radiotherapy. Future studies should lead to development of CSC-targeted therapies for cancer treatment.

Keywords

• -

Solid tümörlerde ve lösemilerde kanser kök hücreleri

Öz

Kanser kök hücreleri (KKH) tümörün başlangıcından sorumlu olan ve tümör dokusundaki çok sayıda farklılaşmış hücre topluluğ unu oluşturan hücrelerdir. Aynı özgü sinyal ileti sistemleri KKH'lerin ve normal kök hücrelerinin kendi-kendini yenileme ve/veya farklılaşmasında fonksiyonel rol oynarlar. Aralarındaki başlıca fark; KKH'lerde aynı sinyal ileti sistemlerinin düzenlenmesi değişmektedir. Son çalışmalarla KKH'lerin ilaç ve radyasyon tedavisine dirençli oldukları gösterilmiştir. Gelecekteki çalışmalar kanserin tedavisi için KKH'leri hedef alan tedavilerin geliştirilmesine öncülük edecektir.

Anahtar Kelimeler

• Kanser kök hücresi, kanser kök hücresi belirteçleri, normal kök hücre

References

1. 1. Kakarala M, Wicha MS. Cancer stem cells: implications for cancer treatment and prevention. Cancer J 2007;13(5):271-5.
2. 2. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001;414(6859):105-11.
3. 3. Wu XZ. Origin of cancer stem cells: the role of selfrenewal and differentiation. Ann Surg Oncol 2008;15(2):407-14.
4. 4. Cho RW, Clarke MF. Recent advances in cancer stem cells. Curr Opin Genet Dev 2008;18(1):48-53.
5. 5. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997;3(7):730-7.
6. 6. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 2003;100(7):3983-8.
7. 7. Singh SK, Clarke ID, Hide T, Dirks PB. Cancer stem cells in nervous system tumors. Oncogene 2004;23(43):7267-73.
8. 8. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature 2004;432(7015):396-401.

9. 9. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res 2007;67(3):1030-7.
10. 10. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A 2007;104(3):973-8.
11. 11. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature 2007;445(7123):111-5.
12. 12. Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, et al. Identification of cells initiating human melanomas. Nature 2008;451(7176):345-9.
13. 13. Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R, et al. Ovarian cancer side population defines cells with stem celllike characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci U S A 2006;103(30):11154-9.
14. 14. Al-Hajj M, Clarke MF. Self-renewal and solid tumor stem cells. Oncogene 2004;23(43):7274-82. 15. Wicha MS. Cancer stem cell heterogeneity in hereditary breast cancer. Breast Cancer Res 2008;10(2):105.
15. 16. Mimeault M, Hauke R, Mehta PP, Batra SK. Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers. J Cell Mol Med 2007;11(5):981-1011.
16. 17. Ailles LE, Weissman IL. Cancer stem cells in solid tumors. Curr Opin Biotechnol 2007;18(5):460-6.
17. 18. Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A 2007;104(24):10158-63.
18. 19. O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007;445(7123):106-10.
19. 20. Woodward WA, Sulman EP. Cancer stem cells: markers or biomarkers? Cancer Metastasis Rev 2008;27(3):459-70.