The Role Of Chemokine CXCL14 In Breast Cancer And Its Significance

Background:CXCL14, also known as breast and kidney-expressed chemokine (BRAK), was initially identified as a chemokine highly expressed in the kidney and breast. The exact function of CXCL14in human breast cancer is still unclear although it has been testified to play an anti-tumor role in other tumors, including head and neck squamous cell carcinoma (HNSCC), lung cancer, prostate cancer, and so on.Method:In this study, we tried to demonstrate the relationship between CXCL14and breast cancer. CXCL14expressions were detected by reverse transcription-PCR and Western blot in2normal breast epithelial cell lines and6human breast cancer cell lines. The effects of CXCL14on the proliferation and invasion in vitro were tested using the CXCL14-overexpressing cells (MDA-MB-231HM-CXCL14) which were established by stable transfection. We established an orthotopic xenograft tumor model in SCID mice using the MDA-MB-231HM-CXCL14cells and explored the influence of CXCL14overexpression on tumor growth and metastasis in vivo. Furthermore, we detected the protein level of CXCL14in208breast cancer patients by immunohistochemistry and discuss the correlation between CXCL14and the prognosis of breast cancer.Result:CXCL14mRNA expression is lower in breast cancer cell lines, and MDA-MB-231HM express lowest levels of CXCL14mRNA. Overexpression of CXCL14inhibited cell proliferation and invasion in vitro and attenuated xenograft tumor growth, lung metastasis and intratumor microvescular density (MVD) in vivo. CXCL14protein level is positively correlated to the overall survival of all patients as well as the patients with lymph node metastasis. And it has a negative correlation with the lymph node metastasis.Conclusion:Our study showed for the first time that CXCL14is a negative regulator of growth and metastasis in breast cancer. The re-expression or up-regulation of this gene may provide a novel strategy in breast cancer therapy in the future.