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Mol Carcinog. 2019 Jan;58(1):144-155. doi: 10.1002/mc.22916. Epub 2018 Oct 16.

CXCR7 is not obligatory for CXCL12-CXCR4-induced epithelial-mesenchymal transition in human ovarian cancer.

Zheng N1,2, Liu W1,2, Chen J1,2, Li B1,2, Liu J1,2, Wang J3, Gao Y1,2, Shao J1,2, Jia L1,2.

Author information

1
Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China.
2
Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, China.
3
Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, Fujian Medical University, Fuzhou, Fujian, China.

Abstract

Although the CXCL12-CXCR4/CXCR7 chemokine axis is demonstrated to play an integral role in tumor progression, the controversy exists and the role of CXCL12-CXCR4/CXCR7 signaling axis in epithelial-mesenchymal transition (EMT) of human ovarian cancer has not been explored. Here, we showed that in ovarian cancer CXCL12 induced EMT phenotypes including the spindle-like cell morphology, podia and stress fiber formation, a decrease in E-cadherin expression, and increases in mesenchymal N-cadherin and vimentin expressions. These effects of CXCL12 could be antagonized by the CXCR4 antagonist AMD3100, but not by the anti-CXCR7 antibody. The expressions of the EMT markers were significantly down-regulated by the CXCR4 siRNA, and up-regulated by the pcDNA3.1/CXCR4 plasmid, whereas not affected by the CXCR7 siRNA. Furthermore, intraperitoneal administration of AMD3100 inhibited tumor dissemination and growth in the nude mice inoculated with ovarian IGROV-1 cells with a concomitant reduction in EMT marker expressions. Collectively, these data suggest that CXCR4, rather than CXCR7, plays a key role in CXCL12-activated EMT phenotypes, and targeting the CXCL12-CXCR4 chemokine axis represents a potential therapeutic strategy to prevent ovarian cancer progression.

KEYWORDS:

CXCR4 antagonist; CXCR7 inhibitor; cancer metastasis; epithelial-mesenchymal transition (EMT); human ovarian cancer; the CXCL12-CXCR4/CXCR7 chemokine axis

PMID:
30259564
DOI:
10.1002/mc.22916

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