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J Cancer 2015; 6(10):1049-1057. doi:10.7150/jca.12501 This issue Cite

Research Paper

Staurosporine Induced Apoptosis May Activate Cancer Stem-Like Cells (CD44⁺/CD24^-) in MCF-7 by Upregulating Mucin1 and EpCAM

Na Zhou¹, Rong Wang¹, Yizhuang Zhang¹, Zhen Lei², Xuehui Zhang¹, Ruobi Hu¹, Hui Li¹, Yiqing Mao¹, Xi Wang¹, David M. Irwin^1,3✉, Gang Niu^2✉, Huanran Tan^1✉

1. Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China;
2. Beijing N&N Genetech Company, Beijing, 100082, China;
3. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada

✉ Corresponding authors: Prof. Huanran Tan, Department of Pharmacology Peking University, Health Science Center Physiology Building#232 38 Xue Yuan Road Beijing 100191, China. Tel: +86 10 82802004; Fax: +86 10 82802004; E-mail: tanlabedu.cn, Prof. David M. Irwin, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Tel.: +1-416-978-0519; E-Mail: david.irwinca, Mr Gang Niu, Beijing N&N Genetech Company, Beijing, 100082, China. E-Mail: nngenecom; Tel.: +86-10-6404-7343 (G.N.) More

Abstract

Malignant tumors recur after chemotherapy. A small population of cancer stem-like cells within tumors is now generally considered the prime source of the recurrence. To better understand how cancer stem-like cells induce relapse after fractionated chemotherapy, we examined changes in the CD44⁺/CD24^- cancer stem-like cells population and behavior using the breast cancer cell line MCF-7. Our results show that apart from an increase in the CD44⁺/CD24^- population, proliferation and clone formation, but not migration, were enhanced after recovery from apoptosis induced by two pulses of staurosporine (STS). The distribution of cells in the cell cycle differed between acutely induced apoptosis and fractionated chemotherapy. Sorted CD44⁺/CD24^- stem-like cells from MCF-7 cells recovered from STS treatment possessed greater proliferation abilities. We also observed that mucin1 (MUC1) and Epithelial cell adhesion molecule (EpCAM) were up-regulated in abundance coincidently with proliferation and clone formation enhancement. Our findings suggest that fractionated chemotherapy induced apoptosis could stimulate cancer stem-like cell to behave with a stronger malignant property than cancer cells themselves and MUC1 and EpCAM are important factors involving in this process. By demonstrating changes in cancer stem cell during chemotherapy and identifying the crucial factors, we potentially can target them, to eradicate tumors and overcome cancer relapse.

Keywords: cancer stem cells, apoptosis, chemotherapy, mucin1, EpCAM

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