Interaction between CXCR4 and CCL20 pathways regulates tumor growth

Katia Beider, Michal Abraham, Michal Begin, Hanna Wald, Ido D. Weiss, Ori Wald, Eli Pikarsky, Rinat Abramovitch, Evelyne Zeira, Eithan Galun, Arnon Nagler, Amnon Peled

Research output: Contribution to journalArticlepeer-review

Abstract

The chemokine receptor CXCR4 and its ligand CXCL12 is overexpressed in the majority of tumors and is critically involved in the development and metastasis of these tumors. CXCR4 is expressed in malignant tumor cells whereas its ligand SDF-1 (CXCL12) is expressed mainly by cancer associated fibroblasts (CAF). Similarly to CXCR4, the chemokine CCL20 is overexpressed in variety of tumors; however its role and regulation in tumors is not fully clear. Here, we show that the chemokine receptor CXCR4 stimulates the production of the chemokine CCL20 and that CCL20 stimulates the proliferation and adhesion to collagen of various tumor cells. Furthermore, overexpression of CCL20 in tumor cells promotes growth and adhesion in vitro and increased tumor growth and invasiveness in vivo. Moreover, neutralizing antibodies to CCL20 inhibit the in vivo growth of tumors that either overexpress CXCR4 or CCL20 or naturally express CCL20. These results reveal a role for CCL20 in CXCR4-dependent and -independent tumor growth and suggest a therapeutic potential for CCL20 and CCR6 antagonists in the treatment of CXCR4- and CCL20-dependent malignancies.

Original languageEnglish
Article numbere5125
JournalPLoS ONE
Volume4
Issue number4
DOIs
StatePublished - 2 Apr 2009
Externally publishedYes

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