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Tissue-Specific Stem Cells
Article first published online: 20 SEP 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 10, pages 2309–2319, October 2012
How to Cite
Long, H., Xie, R., Xiang, T., Zhao, Z., Lin, S., Liang, Z., Chen, Z. and Zhu, B. (2012), Autocrine CCL5 Signaling Promotes Invasion and Migration of CD133+ Ovarian Cancer Stem-Like Cells via NF-κB-Mediated MMP-9 Upregulation. STEM CELLS, 30: 2309–2319. doi: 10.1002/stem.1194
Author contributions: H.L and R.X: collection and assembly of data, data analysis and interpretation, and manuscript writing; T.X, Z.Z, S.L., and Z.L: collection and assembly of data and data analysis and interpretation; Z.C. and B.Z.: conception and study design, administrative support, and manuscript writing. H.L. and R.X. contributed equally to this article.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS August 7, 2012.
- Issue published online: 20 SEP 2012
- Article first published online: 20 SEP 2012
- Accepted manuscript online: 7 AUG 2012 09:01AM EST
- Manuscript Accepted: 29 JUN 2012
- Manuscript Received: 24 FEB 2012
- National Nature Science Foundation of China. Grant Numbers: 30901592, 81071772
- Youth Scientist Foundation of Chongqing. Grant Number: CSTC, 2008BA5035
- Century Excellent Talents in University by Ministry of Education of China. Grant Number: NCET-O8-0935
- National Key Basic Research Program of China. Grant Number: 973 program, No. 2010CB529404
- Cancer stem cells;
The concept of cancer stem cells (CSCs) proposes that solely CSCs are capable of generating tumor metastases. However, how CSCs maintain their invasion and migration abilities, the most important properties of metastatic cells, still remains elusive. Here we used CD133 to mark a specific population from human ovarian cancer cell line and ovarian cancer tissue and determined its hyperactivity in migration and invasion. Therefore, we labeled this population as cancer stem-like cells (CSLCs). In comparison to CD133− non-CSLCs, chemokine CCL5 and its receptors, CCR1, CCR3, and CCR5, were consistently upregulated in CSLCs, and most importantly, blocking of CCL5, CCR1, or CCR3 effectively inhibits the invasive capacity of CSLCs. Mechanistically, we identified that this enhanced invasiveness is mediated through nuclear factor κB (NF-κB) activation and the consequently elevated MMP9 secretion. Our results suggested that the autocrine activation of CCR1 and CCR3 by CCL5 represents one of major mechanisms underlying the metastatic property of ovarian CSLCs. STEM CELLS2012;30:2309–2319