Open AccessAutocrine CCL5 Signaling Promotes Invasion and Migration of CD133 + Ovarian Cancer Stem‐Like Cells via NF‐κB‐Mediated MMP‐9 Upregulation
Author(s) -
Long Haixia,
Xie Rongkai,
Xiang Tong,
Zhao Zhongquan,
Lin Sheng,
Liang Zhiqing,
Chen Zhengtang,
Zhu Bo
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1194
Subject(s) - biology , autocrine signalling , cancer research , cancer stem cell , population , downregulation and upregulation , ccr1 , ccl5 , cancer , ovarian cancer , metastasis , stem cell , chemokine receptor , chemokine , microbiology and biotechnology , immunology , receptor , inflammation , t cell , medicine , il 2 receptor , biochemistry , genetics , environmental health , immune system , gene
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. S TEM C ELLS 2012;30:2309–2319