Systemic chemokine levels in breast cancer patients and their relationship with circulating menstrual hormones

Abstract

Introduction The chemokines Stromal Cell-Derived Factor-1 alpha (SDF-1 alpha/CXCL12) and Monocyte Chemotactic Protein-1 (MCP-1/CCL2) have been implicated in breast cancer progression. We recently reported elevated systemic MCP-1 in breast cancer patients. This study investigated circulating levels of SDF-1 alpha in breast cancer patients, and addressed potential hormonal regulation of these two potent chemokines. Methods SDF-1 alpha levels were determined by ELISA in 114 breast cancer patients and 85 controls, and correlated with clinical data. Blood samples were collected from 36 healthy premenopausal volunteers weekly for four weeks to measure Luteinising Hormone (LH), Follicular Stimulating Hormone (FSH), Oestradiol and Progesterone using a Bayer ADVIA(A (R)) Centaur Immunoassay system, in parallel with SDF-1 alpha and MCP-1. CXCL12 expression was determined using RQ-PCR in primary tumour stromal cells (n = 16) harvested at surgery. Results Plasma SDF-1 alpha was significantly higher in breast cancer patients than age-matched controls and had a significant correlation with tumour grade and epithelial subtype. Investigation of menstrual variations of these chemokines revealed lower SDF-1 alpha levels in the mid-luteal phase of the menstrual cycle and a significant positive correlation with circulating Oestradiol. MCP-1 levels showed no correlation with menstrual hormones. There was a trend towards increased CXCL12 expression in tumour compared to normal stromal cells. Conclusions The elevated level of SDF-1 alpha detected in breast cancer patients, and it's correlation with prognostic indicators, highlights the importance of this chemokine in disease progression. Elucidation of factors influencing chemokine secretion supports clarification of their role in tumourigenesis.