Meme Kanseri Kök Hücreleri ve Demir Bağımlılığı

ÖzGiriş: Meme kanseri dünya çapında kadınlarda görülen en yaygın kanserdir. Üçlü negatif ve meme kanseri (TNBC) ve üçlü pozitif meme kanseri (TPBC) gibi farklı alt tiplerde kategorilere ayrılan heterojen bir hastalıktır. TNBC’ler ve TPBC’ler farklı genetik altyapıları gösterirler ve bu meme kanserinde terapötik çeşitliliğe yol açar. Bu çeşitliliğin üstesinden gelmek için hücrelerin tümörijenik özelliklerini bilmek çok önemlidir. Yöntemler: Flowsitometriden faydalanılarak floresan bir prob olan calcein-AM yardımıyla hücreiçi demir seviyelerini ölçmek için TPBC hücre hatları BT474, HCC1954 ve TNBC hücre hatları MDA-MB-435, MDA-MB-231, Hs578T kullanıldı. Meme kanseri kök hücreleri (BCSCs) hücre hatlarında CD44+/CD24- ‘ün yüzey ekspresyonu ile tanımlandı. Bulgular: Burada TNBC’lerinTPBC’lerden daha fazla bazal demire ve BCSC’ye sahip olduğu gösterilmiştir. Demir ilavesi TPBC’lerde BCSC populasyonunun artmasını sağlamıştır. Sonuç: Demir BCSC’lerin canlılığını idame etmesi bakımından önemli bir elementtir.

Breast Cancer Stem Cells and Iron Dependency

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. Ironaddition provides enrichment of BCSCs in TPBCs. Conclusion: Iron is an important element for maintenance of BCSCs

PDF

___

Raggi C, Gammella E, Correnti M, et al. Dysregulation of iron metabolism in cholangiocarcinoma stem-like cells. Sci Rep. 2017;7:1-12.
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.
Nishitani S, Noma K, Ohara T, et al. Iron depletioninduced downregulation of N-cadherin expression inhibits invasive malignant phenotypes in human esophageal cancer. Int J Oncol. 2016;49:1351–9.
Urano S, Ohara T, Noma K, et al. Iron depletion enhances the effect of sorafenib in hepatocarcinoma. Cancer BiolTher. 2016;17:648–56.
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.
Cui J, Hollmen M, Li L, et al. New use of an old drug: nhibition of breast cancer stem cells by benztropinemesylate. Oncotarget. 2017;8:1007-1022
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 basaltype/“ triple-negative” breast cancer cell lines growing in vitro. Breast Cancer Res Treat. 2007;105:319-26.
Gupta PB, Onder TT, Jiang G, et al. Identification of selective inhibitors of cancer stem cells by highthroughput screening. Cell. 2009;138:645-59.
Sun M, Lou W, Chun JY, et al. Sanguinarine suppresses prostate tumor growth and inhibits survivinexpression. Genes Cancer. 2010;1:283-92.
Marx C, Berger C, Xu F, et al. Validated highthroughput screening of drug-like small molecules for inhibitors of ErbB2 transcription. Assay Drug Dev Technol. 2006;4:273-84.
Hamai A, Caneque T, Müller S, et al. An iron hand over cancer stem cells. Autophagy. 2017;13:1465-6.
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. ExpOncol. 2017;39:203-11
Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008;8:755-68.
Nguyen LV, Vanner R, Dirks P, Eaves CJ. Cancer stem cells: an evolving concept. Nat Rev Cancer. 2012;12:133-43.
Karnoub AE, Dash AB, Vo AP, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449:557-63.
Wahba HA, El-Hadaad HA. Current approaches in treatment of triple-negative breast cancer. Cancer Biol Med. 2015;12:106-16.
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.
Sevimli TS, Sevimli M, Ozcelik N. Protein expression changes in breast cancer and their importance. Dicle Med J 2013;40:161-8.
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.
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.
Ozer U. Copper enriches efficacy of Dp44mT in breast cancer cells. Turk J Biol. 2016;40:1185-91.
Ozer U. The role of iron on breast cancer stem-like cells. Cell Mol Biol. 2016;62:25-30.
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.
Ellis S, Sexton DW, Steverding D. Trypanotoxic activity of thiosemicarbazone iron chelators. ExpParasitol. 2015;150:7-12.
Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149:1060–72.
Merlot AM, Kalinowski DS, Richardson DR. Novel chelators for cancer treatment: where are we now?.Antioxid Redox Signal. 2013;18:973–1006.
Bystrom LM, Rivella S. Cancer cells with irons in the fire. Free RadicBiol Med. 2015;79:337–42.
Torti SV, Torti FM. Iron and cancer: more ore to be mined. Nat Rev Cancer. 2013;13:342–55.
Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochem J. 2011;434:365–81.
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.
Meacham CE, Morrison SJ. Tumour heterogeneity and cancer cell plasticity. Nature. 2013;501:328-37.
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.
Colak S, Medema JP. Cancer stem cells – important players in tumor therapy resistance. Febs J. 2014;281:4779-91.
Iancu G, Vasile D, Iancu RC, DaviToiu DV. "Triple positive" breast cancer - a novel category? Rom J MorpholEmbryol. 2017;58:21-6.
Shah D, Osipo C. Cancer stem cells and HER2 positive breast cancer: the story so far. Genes and Diseases. 2016;3:114-23.
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.