Expression and Role in the Proliferation of the Colony-Stimulating Factor-1 Receptor in Breast Cancer Cells

Background: Breast cancer is the most prevalent cancer in non-smoking women and the second leading cause of cancer-related deaths in western countries. The Colony- Stimulating Factor 1 (CSF1) and its receptor CSF1R physiologically regulate the monocyte/macrophage system, trophoblast implantation and breast development. An abnormal expression of CSF1R, associated or not with that of CSF1, has been also documented in several human epithelial tumors, including breast carcinomas. Despite the fact that the expression of both CSF1 and CSF1R strongly correlates with poor prognosis of breast cancer, scanty data have been obtained on CSF1R signaling in neoplastic cells. Methods: 17 breast cancer cell lines of different molecular classes (i.e. presence/absence of estrogen or progesterone receptors or HER2 over-expression) were used. Results: All 17 cell lines tested but one expressed cell surface CSF1R protein or CSF1R mRNA although to different extents. Moreover, in silico analysis from microarray data of 49 breast cancer cell lines indicated that CSF1R mRNA was consistently expressed, irrespectively of molecular class. siRNA silencing of CSF1R or blocking CSF1 with an anti-serum in SKBR3 cells markedly decreased, while exposure of MDAMB468 cells to CSF1 increased, CSF1-dependent cell proliferation. We also found that ERK1/2, c-Jun, Cyclin D1 and c-Myc are CSF1/CSF1R targets in breast cancer cells. Imatinib decreased cell prolifaration in the presence of CSF1 of a number of cell lines. Conclusions: Taken together, the results reported here indicate that CSF1 and CSF1R are determinant for the proliferation of breast cancer cells and point to CSF1R as a possible new target for breast cancer therapy.