Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer
Technical Report,15 Sep 2015,14 Sep 2018
University of Arizona Tucson United States
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There is an urgent need to develop both new approaches to the treatment of prostate cancer. Analysis of human prostate samples demonstrates that a specific signaling pathway, the Pim kinase pathway is elevated in the fibroblasts from human prostate tumors. To understand the role of myofibroblastcancer associated fibroblasts CAFs in transformation, the laboratory proposes 1 to examine in detail the proteins secreted by the stroma that can modulate epithelial growth, 2 to evaluate the ability of Pim inhibitors to block this activity, and 3 to investigate whether exosomes can potentially be used asa biomarker of Pim kinase inhibitor activity. Results to date demonstrate that Pim increases in prostate stromal cells enhances protein synthesis, the levels of important transcription factors, long non-coding RNAs, and tyrosine kinases associated with signal transduction as well increased exosomal transfer both in cells co-cultured and when conditioned media is placed on prostate epithelial cells. These changes are blocked by the addition of Pim inhibitors. These results suggest that the Pim protein kinase can regulate stromal cell biology to modulate epithelial growth and that inhibitors of this protein kinase have the potential to block this process and thus inhibit tumor growth.
- Medicine and Medical Research