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 TGF beta 1, was also investigated. Methods: Circulating levels of CCL5 and TGF beta 1 were measured in 102 breast cancer patients and 66 controls using ELISA. Gene expression levels (CCL5, CCR5, TGF beta 1, TGF beta RII) 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: TGF beta 1 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 TGF beta 1 (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 TGF beta 1 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 TGF beta 1 in breast cancer. (C) 2011 Elsevier Ltd. All rights reserved.