Breast Cancer Stem Cells and Iron Dependency

Year 2018, Volume: 45 Issue: 2, 195 - 200, 15.06.2018

Ufuk Ozer

https://doi.org/10.5798/dicletip.419307

Abstract

Objectives:
Among woman, breast cancer is the most prevalent cancer worldwide. It is
composed of various cell types that are classified into different subtypes such
as triple negative breast cancer (TNBC), triple positive breast cancer (TPBC).
TNBCs and TPBCs represent distinct genetic background, thereby leading to
therapeutic diversity in breast cancer. It is critical to know their
tumorigenic properties to overcome the diversity.

Methods:
TPBC cell lines; BT474, HCC1954 and TNBC cell lines; MDA-MB-435, Hs578T,
MDA-MB-231 were used to measure intracellular iron levels via a fluorescent
probe, calcein-AM, utilizing flow cytometry. Breast cancer stem cells (BCSCs)
are detected by surface expression of CD44+/CD24- markers in the lines.

Results:
Here, it has shown that TNBCs have higher basal levels of iron and population
of BCSCs than TPBCs. Iron addition provides enrichment of BCSCs in TPBCs.

Conclusion:
Iron is an important element for maintenance of BCSCs. 

Keywords

Breast cancer stem cells, iron, TNBC

References

• 1. Ghoncheh M, Pournamdar Z, Salehiniya H. Incidence and mortality and epidemiology of breast cancer in the world. Asian Pac J Cancer Prev. 2016;17:43-6.
• 2. Shah D, Osipo C. Cancer stem cells and HER2 positive breast cancer: the story so far. Genes and Diseases. 2016;3:114-23.
• 3. Iancu G, Vasile D, Iancu RC, DaviToiu DV. "Triple positive" breast cancer - a novel category? Rom J Morphol Embryol. 2017;58:21-6.
• 4. Colak S, Medema JP. Cancer stem cells – important players in tumor therapy resistance. Febs J. 2014;281:4779-91.
• 5. Malanchi I, Santamaria-Martinez A, Susanto E, et al. Interactions between cancer stem cells and their niche govern metastatic colonization. Nature. 2012;481:85-9.
• 6. Meacham CE, Morrison SJ. Tumour heterogeneity and cancer cell plasticity. Nature. 2013;501:328-37.
• 7. Lawen A, Lane DJ. Mammalian iron homeostasis in health and disease: uptake, storage, transport, and molecular mechanisms of action. Antioxid Redox Signal. 2013;18:2473–507.
• 8. Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochem J. 2011;434:365–81.
• 9. Torti SV, Torti FM. Iron and cancer: more ore to be mined. Nat Rev Cancer. 2013;13:342–55.
• 10. Bystrom LM, Rivella S. Cancer cells with irons in the fire. Free Radic Biol Med. 2015;79:337–42.
• 11. Merlot AM, Kalinowski DS, Richardson DR. Novel chelators for cancer treatment: where are we now?. Antioxid Redox Signal. 2013;18:973–1006.
• 12. Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149:1060–72.
• 13. Ellis S, Sexton DW, Steverding D. Trypanotoxic activity of thiosemicarbazone iron chelators. Exp Parasitol. 2015;150:7-12.
• 14. Salis O, Bedir A, Kilinc V, Alacam H, Gulten S, Okuyucu A. The anticancer effects of desferrioxamine on human breast adenocarcinoma and hepatocellular carcinoma cells. Cancer Biomark. 2014;14:419-26.
• 15. Ozer U. The role of iron on breast cancer stem-like cells. Cell Mol Biol. 2016;62:25-30.
• 16. Ozer U. Copper enriches efficacy of Dp44mT in breast cancer cells. Turk J Biol. 2016;40:1185-91.
• 17. Riaz M, van Jaarsveld MT, Hollestelle A, et al. miRNA expression profiling of 51 human breast cancer cell lines reveals subtype and driver mutation-specific miRNAs. Breast Cancer Res. 2013;15:R33.
• 18. Kucukoner M, Kaplan MA, Inal A, et al. Approach to hypersplenism due to splenic metastasis of breast cancer: A case report. Dicle Med J. 2012;39:117-20.
• 19. Sevimli TS, Sevimli M, Ozcelik N. Protein expression changes in breast cancer and their importance. Dicle Med J 2013;40:161-8.
• 20. Dai X, Cheng H, Bai Z, Li J. Breast cancer cell line classification and its relevance with breast tumor subtyping. J Cancer. 2017;8:3131-41.
• 21. Wahba HA, El-Hadaad HA. Current approaches in treatment of triple-negative breast cancer. Cancer Biol Med. 2015;12:106-16.
• 22. Karnoub AE, Dash AB, Vo AP, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449:557-63.
• 23. Nguyen LV, Vanner R, Dirks P, Eaves CJ. Cancer stem cells: an evolving concept. Nat Rev Cancer. 2012;12:133-43.
• 24. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008;8:755-68.
• 25. Chekhun VF, Lukianova NY, Chekhun SV, et al. Association of CD44+CD24-/low with markers of aggressiveness and plasticity of cell lines and tumors of patients with breast cancer. Exp Oncol. 2017;39:203-11.
• 26. Hamai A, Caneque T, Müller S, et al. An iron hand over cancer stem cells. Autophagy. 2017;13:1465-6.
• 27. Marx C, Berger C, Xu F, et al. Validated high-throughput screening of drug-like small molecules for inhibitors of ErbB2 transcription. Assay Drug Dev Technol. 2006;4:273-84.
• 28. Sun M, Lou W, Chun JY, et al. Sanguinarine suppresses prostate tumor growth and inhibits survivin expression. Genes Cancer. 2010;1:283-92.
• 29. Gupta PB, Onder TT, Jiang G, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009;138:645-59.
• 30. Finn RS, Dering J, Ginther C, et al. Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/“triple-negative” breast cancer cell lines growing in vitro. Breast Cancer Res Treat. 2007;105:319-26.
• 31. Cui J, Hollmen M, Li L, et al. New use of an old drug: inhibition of breast cancer stem cells by benztropine mesylate. Oncotarget. 2017;8:1007-1022.
• 32. Ohara T, Noma K, Urano S, et al. A novel synergistic effect of iron depletion on antiangiogenic cancer therapy. Int J Cancer. 2013;132:2705–13.
• 33. Urano S, Ohara T, Noma K, et al. Iron depletion enhances the effect of sorafenib in hepatocarcinoma. Cancer Biol Ther. 2016;17:648–56.
• 34. Nishitani S, Noma K, Ohara T, et al. Iron depletion-induced downregulation of N-cadherin expression inhibits invasive malignant phenotypes in human esophageal cancer. Int J Oncol. 2016;49:1351–9.
• 35. Ninomiya T, Ohara T, Noma K, et al. Iron depletion is a novel therapeutic strategy to target cancer stem cells. Oncotarget. 2017;8:98405-416.
• 36. Raggi C, Gammella E, Correnti M, et al. Dysregulation of iron metabolism in cholangiocarcinoma stem-like cells. Sci Rep. 2017;7:1-12.