Silencing of CXCR4 blocks progression of ovarian cancer and depresses canonical Wnt signaling pathway.

OBJECTIVE: CXC chemokine receptor 4 (CXCR4) was considered to be an important factor in cancer cell metastasis. This study was aimed to examine the expression of CXCR4 in ovarian cancer and determine the functions and the possible mechanisms of CXCR4 in the progression of ovarian cancer.

METHODS: CXC chemokine receptor 4 messenger RNA expression in normal ovarian tissues, malignant epithelial ovarian tumors, and 3 ovarian cancer cell lines was analyzed. Immunohistochemical analysis was used to detect the protein expression of CXCR4 and β-catenin in normal and malignant ovarian tissues. The effect of CXCR4 inhibition on cell proliferation and invasion was determined.

RESULTS: CXC chemokine receptor 4 was highly expressed in malignant ovarian tumors and ovarian cancer cell lines, and the different expression of CXCR4 was observed between the ovarian cancers with lymph node metastasis and without lymph node metastasis. Furthermore, The CXCR4 expression was correlated with β-catenin expression in ovarian tissues. Moreover, knockdown of CXCR4 could obviously reduce proliferation and invasion of ovarian cancer cell and inhibit Wnt target genes and mesenchymal markers such as vimentin and SLUG expression.

CONCLUSIONS: CXC chemokine receptor 4 plays a critical role in the metastasis of human ovarian cancer possibly through modulating the Wnt/β-catenin pathway. CXC chemokine receptor 4 is a potential therapeutic target for treatment of ovarian cancer.