Autocrine CCL5 Signaling Promotes Invasion and Migration of CD133+ Ovarian Cancer Stem-Like Cells via NF-κB-Mediated MMP-9 Upregulation§

Authors

  • Haixia Long,

    1. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China
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  • Rongkai Xie,

    1. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China
    2. Department of Obstetrics and Gynecology, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China
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  • Tong Xiang,

    1. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China
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  • Zhongquan Zhao,

    1. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China
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  • Sheng Lin,

    1. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China
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  • Zhiqing Liang,

    1. Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China
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  • Zhengtang Chen,

    Corresponding author
    1. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China
    • Zhengtang Chen, Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, Peoples Republic of China

      Bo Zhu, Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, Peoples Republic of China

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    • Telephone: 86-23-68755626; Fax: 86-23-68755626

  • Bo Zhu

    Corresponding author
    1. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China
    • Zhengtang Chen, Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, Peoples Republic of China

      Bo Zhu, Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, Peoples Republic of China

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    • Telephone: 86-23-68774389; Fax: 86-23-68774389


  • 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.

Abstract

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

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