SDF-1-CXCR4 Axis Functions Through p38-MAPK Signaling to Drive Breast Cancer Progression and Metastasis

摘要

The primary long-term objective of this research is to understand how chemokine signaling through MAPK influences progression of breast carcinoma cells to a hormone-independent, endocrine therapy resistant and metastatic phenotype. Our preliminary evidence demonstrates that over expression of CXCR4 in breast carcinoma cells leads to a hormone independent phenotype in vivo. It was also determined by our lab that human mesenchymal stem cells in contact with breast cancer cells (MCF7 cell line) could induce proliferation and lead to hormone independent tumors in vivo. Upon analysis of these tumors by real- time PCR, it was found that the MSC containing tumors had increased gene transcription of progesterone receptor as well as SDF-1 indicating ER crosstalk. Future studies are planned to look more closely at the mechanisms involved in this MSC- tumor cell interaction, specifically identifying a role for SDF-1. We propose SDF-1 is the primary factor involved, either being secreted by the MSCs or the MSCs are stimulating its production in the carcinoma cells themselves. Future plans involve using MSCs as source for SDF-1 to test previously outlined objectives.