CXCL5 Secreted From Adipose Tissue-derived Stem Cells Promotes Proliferation Of Cancer Cells

Background and PurposeObesity is a major risk factor for a variety of diseases including cancers,diabetes and cardiovascular diseases,and particularly associated with an increased risk of developing breast cancer in postmenopausal females.Obese subjects have more aggressive breast tumors and higher risk of recurrence;a high body mass index has a predictive value for worse outcome in both pre-and post-menopausal breast cancer patients.In postmenopausal breast cancer patients,more than 50% of deaths are likely attributable to obesity.Accumulating evidence suggests that adipose tissue exerts facilitatory effects on breast tumor initiation and progression through both paracrine and endocrine pathways,and that the adipose tissue-derived stem cell(ASC)is likely the major cell type responsible for the tumorigenesis and development.However,it remains unknown how ASCs exert their effects.MethodsHere,in cultured breast cancer cell lines including estrogen receptor(ER)-positive MCF-7 cells and ER-negative MDA-MB-231 cells,we examined effects of isolated ASCs from human breasts and abdomen versus human fibroblast cell line WI-38 as well as their medium of co-culture with the breast cancer cells on breast tumor proliferation.On this basis,we further identified the expression of 174 cytokines and observed effects of neutralization of CXCL5 in the co-culture medium of ASCs and tumor cells with human CXCL5 monoclonal antibody on the actions of ASCs.ResultsOur results showed that ASCs significantly increased the numbers of both breast cancer cell lines compared to the vehicle and WI-38 controls.Similarly,the co-culture medium of ASCs with the breast cancer cells had potent effects on the tumor cell proliferation.In the co-culture medium of ASCs but not WI-38 with the breast cancer cells,CXCL5 levels were increased significantly.Finally,depletion of CXCL5 with its specific antibody in ASC-conditioned medium blocked the stimulatory effect of ASCs but not WI-38 on the proliferation of breast cancer cells.ConclusionsOur results indicate for the first time that ASC-secreted CXCL5 is a key factor promoting breast tumor cell proliferation.The interactions between tumors and adipose tissues enhance CXCL5 expression,CXCL5 could be a potential therapeutic target of breast cancer.