期刊
STEM CELLS
卷 30, 期 10, 页码 2309-2319出版社
WILEY
DOI: 10.1002/stem.1194
关键词
Cancer stem cells; CCL5; Invasion; Migration; Ovarian
资金
- National Nature Science Foundation of China [30901592, 81071772]
- outstanding Youth Scientist Foundation of Chongqing [CSTC, 2008BA5035]
- Century Excellent Talents in University by Ministry of Education of China [NCET-O8-0935]
- National Key Basic Research Program of China (973 program) [2010CB529404]
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 ?B (NF-?B) 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;30:23092319
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