Targeting the Neural Microenvironment in Prostate Cancer
Technical Report,30 Sep 2015,29 Sep 2016
BAYLOR COLLEGE OF MEDICINE HOUSTON United States
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Prostate cancer PCa remains the most common malignancy and the second leading cause of cancer-related death for men in the United States. Recent studies have shown significant interactions between nerves and adjacent cancer cells that promote cell survival, proliferation and migration of PCa cells. Our studies of laser captured prostate cancer reactive stroma have shown that among the most upregulated genes is glial cell line-derived neurotrophic factor GDNF, which is expressed by peripheral nerves. GDNF binds to RET, a receptor tyrosine kinase, in conjunction with its co-receptor GFR1 GFRA1 and activates cellular signaling. Both RET and GFRA1 are expressed on all PCa cell lines tested and RET protein is increased in PCa. Studies in pancreatic cancer strongly implicate GDNF as a key factor promoting perineural migration. We will test the hypothesis that GDNF is expressed by nerves and that it acts on RETGFRA1 in adjacent PCa cells to promote proliferation and invasion and inhibit apoptosis and that disruption of this signaling cascade will inhibit PCa progression in vivo.
- Medicine and Medical Research