Systemic chemokine levels in breast cancer patients and their relationship with circulating menstrual hormones.
BACKGROUND
The chemokines Stromal Cell-Derived Factor-1alpha (SDF-1alpha/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-1alpha in breast cancer patients, and addressed potential hormonal regulation of these two potent chemokines.


METHODS
SDF-1alpha 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 Centaur Immunoassay system, in parallel with SDF-1alpha and MCP-1. CXCL12 expression was determined using RQ-PCR in primary tumour stromal cells (n = 16) harvested at surgery.


RESULTS
Plasma SDF-1alpha 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-1alpha 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-1alpha 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.
Department of Surgery, Clinical Science Institute, National University of Ireland, Galway, Galway, Ireland.
Shirley M
SM
Potter
Roisin M
RM
Dwyer
Catherine E
CE
Curran
Emer
E
Hennessy
Kate A
KA
Harrington
Damian G
DG
Griffin
Michael J
MJ
Kerin
D000328:Adult; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology; D018932:Chemokine CCL2 / Q000097:blood*; D054377:Chemokine CXCL12 / Q000097:blood*; D018925:Chemokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D015870:Gene Expression; D042341:Gonadal Hormones / Q000097:blood*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008597:Menstrual Cycle / Q000502:physiology; D008875:Middle Aged; D011374:Progesterone / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction
C111835:CCL2 protein, human; C515255:CXCL12 protein, human; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D018925:Chemokines; D042341:Gonadal Hormones; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone