Role of CCL5 in invasion, proliferation and proportion of CD44+/CD24− phenotype of MCF-7 cells and correlation of CCL5 and CCR5 expression with breast cancer progression

This study was undertaken to observe the effects and possible mechanism of CC chemokine ligand 5 (CCL5) on invasion, proliferation and percentage of CD44+/CD24− subpopulation of human breast cancer line MCF-7 and to investigate the correlation of expression levels of CCL5 and its receptors with the progression of breast cancer. We used real-time RT-PCR to detect the expression levels of CCL5 and its receptors CCR5, CCR1 and CCR3 in 36 breast cancer specimens of different TNM stage and their corresponding normal breast tissue. CCL5 expression and invasive ability of four human breast cancer cell lines MCF-7, SK-BR-3, T-47D and MDA-MB-231 were analyzed by real-time RT-PCR and cell invasion assay, respectively. Effects of recombinant human CCL5 (rhCCL5) on cell proliferation and percentage of the CD44+/CD24− subpopulation in MCF-7 cells were analyzed respectively by MTT assay and flow cytometry. We also used cell invasion assay to detect the invasive ability of both CD44+/CD24− and CD44+/CD24+ subpopulations of MCF-7 cells treated with rhCCL5 and/or CCR5 monoclonal antibody. Our results revealed that CCL5 and CCR5 expression were higher in breast cancer tissue than those in their corresponding normal tissue and breast cancer tissue with higher TNM stage contained more CCL5 mRNA. In addition, CCR5 expression and invasive ability of CD44+/CD24− subpopulation were higher than those of CD44+/CD24+ subpopulation of MCF-7 cells. Moreover, treatment of rhCCL5 increased the proportion of CD44+/CD24− cells and the proliferation of MCF-7 cells. Induction of rhCCL5 increased the cell invasive ability of both CD44+/CD24− and CD44+/CD24+ cells, which could be partially antagonized by CCR5 monoclonal antibody. Collectively, our data show that CCL5 increased the proportion of CD44+/CD24− subpopulation and induced invasion and proliferation of MCF-7 cells, and expression of CCL5 and CCR5 in breast cancer tissue was positively correlated with breast cancer progression.