Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion.

摘要

We hypothesize that exosomes secreted by advanced prostate cancer cells groom stromal cells at pre-metastatic sites to render the bone microenvironment more favorable for metastatic growth. We propose to test the hypothesis that exosomes derived from advanced stage prostate cancer exert a pro-metastatic influence on bone stromal cells. Aim No. 1: We will perform a quantitative comparison of changes in the structure and cargo of exosomes derived from early versus advanced prostate cancer cell lines to identify mechanisms of action. Aim No. 2: We will profile alterations in potential target stromal cells upon exposure to early versus late prostate cancer exosomes to determine the effect on the metastatic microenvironment. We have made substantial progress towards establishing the protocols needed for robust and quantitative analysis. Testing this hypothesis has direct relevance towards an understanding of the often lethal complications of prostate cancer, manifested in extensive and painful metastasis of the bone.