Targeting Quiescence in Prostate Cancer
Technical Report,15 Sep 2016,14 Sep 2017
University of Michigan Ann Arbor United States
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A major problem in prostate cancer is finding and eliminating the non-proliferating or quiescent cancer cells. This is because early in prostate cancer, a small number of cancer cells metastasize to other tissues such as the bone, where they can lay dormant for years. Most chemotherapies target actively dividing cancer cells causing primary tumor shrinkage, but leave behind quiescent cancer cells which may seed new, more aggressive and chemo-resistant cancers at a later date. During this second year of funding, we have discovered that PCa cells that metastasize to the bone exhibit dramatically different cell cycle characteristics from those in the liver, suggesting signals from the bone are key to regulating PCa cell cycle and dormancy. We therefore tested signals from the marrow environment and determined how they influence the proliferation vs. quiescence decision in PCa cells. To examine how the bone marrow environment may promote PCa dormancy, we performed transcriptome analysis on mouse bone marrow cells with dormant PCa DTCs vs. recurrent PCa. We have identified secreted host marrow signals that may promote dormancy in PCa cells for study in the next funding period. We will also examine how these signals may modulate the effect of chemotherapies on PCa cell cycle regulation.
- Medicine and Medical Research