Relationship between CCL5 and transforming growth factor-β1 (TGFβ1) in breast cancer

Purpose Investigate circulating CCL5 in breast cancer patients and healthy controls, along with gene expression levels in corresponding tumour tissue and isolated primary stromal cells. Hormonal control of CCL5, and a potential relationship with TGFβ1, was also investigated. Methods Circulating levels of CCL5 and TGFβ1 were measured in 102 breast cancer patients and 66 controls using ELISA. Gene expression levels (CCL5, CCR5, TGFβ1, TGFβRII) were quantified in corresponding tumour tissue (n = 43), normal tissue (n = 16), and isolated tumour (n = 22) and normal (n = 3) stromal cells using RQ-PCR. CCL5 and circulating menstrual hormones (LH, FSH, Oestradiol, Progesterone) were analysed in serum samples from healthy, premenopausal volunteers (n = 60). Results TGFβ1 was significantly higher in breast cancer patients (Mean(SEM) 27.4(0.9) ng/ml) compared to controls (14.9(0.9) ng/ml). CCL5 levels decreased in the transition from node negative (59.6(3.7) ng/ml) to node positive disease (40.5(6.3) ng/ml) and increased again as the number of positive lymph nodes increased (⩾3 positive 50.95(9.8) ng/ml). A significant positive correlation between circulating CCL5 and TGFβ1 (r = 0.423, p < 0.0001) was observed, and mirrored at the gene expression level in tumour tissue from the same patients (r = 0.44, p < 0.001). CCL5, CCR5 and TGFβ1 expression was significantly higher in tumour compared to normal breast tissue (p < 0.001). A significant negative correlation was observed between circulating CCL5, Oestradiol and Progesterone (r = −0.50, r = −0.39, respectively, p < 0.05). Conclusion CCL5 expression is elevated in the tumour microenvironment. The data support a role for hormonal control of circulating CCL5 and also highlight a potentially important relationship between CCL5 and TGFβ1 in breast cancer.This study was supported by funding from the National Breast Cancer Research Institute (NBCRI), a Breast Cancer Ireland Research Fellowship Award (M.C. Hartmann), and the Health Research Board of Ireland (R.M. Dwyer, J. Newell).peer-reviewe