The
chemokines RANTES (CCL5) and MCP-1 (CCL2) were suggested to contribute, independently, to breast
malignancy. In the present study, we asked if the two
chemokines are jointly expressed in clinical samples of
breast cancer patients, and do they interact in
breast tumor cells. We found that
RANTES and MCP-1 were expressed by
breast tumor cells in primary
tumors of
Ductal Carcinoma In Situ and of Invasive
Ductal Carcinoma, but minimally in normal breast epithelial duct cells. The
chemokines were also detected in
metastases and
pleural effusions. Novel findings showed that co-expression of
RANTES and MCP-1 in the same
tumor was associated with more advanced stages of disease, suggesting that
breast tumors "benefit" from interactions between the two
chemokines. Accordingly, MCP-1 significantly promoted the release of
RANTES from endogenous pre-made vesicles, in an active process that depended on
calcium from intracellular and extracellular sources, and on intracellular transport of
RANTES towards exocytosis. Our findings show a
chemokine-triggered release of stored pro-
malignancy chemokine from
breast tumor cells. These observations support a major
tumor-promoting role for co-expression of the
chemokines in breast
malignancy, and agree with the significant association of joint
RANTES and MCP-1 expression with advanced stages of
breast cancer.