Irradiation and chemotherapy drug effects on cancer stem cells (SP) of melanoma B16 and breast adenocarcinoma MCF-7

«Radiation and Risk», 2013, vol. 22, No. 2, pp.67-76

Authors

Matchuk О.N. – Research Assistant, Medical Radiological Research Center of the Russian Ministry of Health, Obninsk. Contacts: 4 Korolyov str., Obninsk, Kaluga region, Russia, 249036. Tel.: (48439) 9-71-88; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Saenko A.S. – Deputy Director, D. Sc., Biol., Prof., Medical Radiological Research Center of the Russian Ministry of Health, Obninsk.

Abstract

The existence of cancer stem cells (CSC), resistant to radiation and chemical exposure is one of the possible causes of cancer recurrence. Since regularities of changes of mentioned cell fraction are not well understood, this study examined relative and absolute CSC number in melanoma B16 and breast cancer MCF-7 stable cultures after low-LET irradiation and anticancer drugs treatment. CSC were identified using side population (SP) technique by the ability to exclude fluorescent dye Hoechst 33342. A linear dependence of the relative number of SP cells on the dose of radiation was found (R=0.98 for B16 and R=0.96 for MCF-7). There was an increase of SP cells absolute number after the exposure; this effect was the most expressed at doses of 5-10 Gy (3 and 5 times in B16 and MCF-7 cultures, respectively, as compared to control, p<0.05 by Mann-Whitney U criterion). We also found that cis-platinum affected the relative and absolute SP cell number stronger than methotrexate (cis-platinum decreased absolute number of SP in 2 times).

Key words
Сancer stem cells, SP, low-LET irradiation, B16, MCF-7.

References

1. Matchuk O. N., Zamulaeva I. A., Selivanova E. I. i dr. Chuvstvitel'nost' kletok SP linii melanomy V16 k deistviiu redko- i plotnoioniziruiushchego izluchenii. Radiats. biologiia. Radioekologiia, 2012, vol. 52, no. 3, pp. 261-267.
2. Britton K.M., Eyre R., Harvey I.J. et al. Breast cancer, side population cells and ABCG2 expression. Cancer Lett., 2012, vol. 323, no. 1, pp. 97-105.

3. Chen K.J., Valencia J.C., Gillet J. et al. Involvement of ABC transporters in melanogenesis and the development of multidrug resistance of melanoma. Pigment Cell Melanoma Res., 2009, vol. 22, no. 6, pp. 740-749.

4. Choi C.H. ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal. Cancer Cell Int., 2005, vol. 4, pp. 5-30.

5. Clarke M.F., Dick J.E., Dirks J.E. et al. Cancer stem cells-perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res., 2006, vol. 66, no. 19, pp. 9339-9344.

6. Feuring-Buske M., Hogge D.E. Hoechst 33342 efflux identifies a subpopulation of cytogenetically normal CD34(+)CD38(-) progenitor cells from patients with acute myeloid leukemia. Blood., 2001, vol. 97, no. 12, pp. 3882-3889.

7. Gottesman M.M., Fojo T., Bates S.E. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat. Rev. Cancer., 2002, vol. 2, pp. 48-58.

8. Hirschmann-Jax C., Foster A.E., Wulf G.G. et al. A distinct "side population" of cells with high drug efflux capacity in human tumor cells. Proc. Natl. Acad. Sci. USA, 2004, vol. 101, pp. 14228-14233.

9. López J., Poitevin A., Mendoza-Martínez V. et al. Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance. BMC Cancer., 2012, vol. 12, no. 48. doi: 10.1186/1471-2407-12-48.

10. Mogi M., Yang J., Lambert J.F. et al. Akt signaling regulates side population cell phenotype via Bcrp1 translocation. J. Biol. Chem., 2003, vol. 278, pp. 39068-39075.

11. Moserle L., Ghisi M., Amadory A., Indraccolo S. Side population and cancer stem cells: therapeutic implications. Cancer Letters, 2010, vol. 288, pp. 1-9.

12. Takada T., Suzuki H., Gotoh Y., Sugiyama Y. Regulation of the cell surface expression of human BCRP/ABCG2 by the phosphorylation state of Akt in polarized cells. Drug. Metab. Dispos., 2005, vol. 33,

pp. 905-909.

13. Woodward W.A., Chen M.S., Behbod F. et al. WNT/β-catenin mediates radiation resistance of mouse mammary progenitor cells. Proc. Natl. Acad. Sci U S A, 2007, vol. 104, no. 2, pp. 618-623.

14. Wu C., Wei Q., Utomo V. et al. Side population cells isolated from mesenchymal neoplasms have tumor initiating potential. Cancer Res., 2007, vol. 67, no. 17, pp. 8216-8222.

15. Zhong Y., Guan K., Zhou C. et al. Cancer stem cells sustaining the growth of mouse melanoma are not rare. Cancer Lett., 2010, vol. 292, no. 1, pp. 17-23.

16. Zhou S., Schuetz J.D., Bunting K.D. 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. Nat. Med., 2001, vol. 7, pp. 1028-1034.

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