Monoamine Oxidase A: A Novel Target for Progression and Metastasis of Prostate Cancer
Technical Report,30 Sep 2012,29 Sep 2015
University of Southern California Los Angeles United States
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The purpose of this project is to investigate the key roles of the monoamine oxidase A MAO A enzyme in the progression and metastasis of prostate cancer PCa. During this funding period, we delineated the functional and mechanistic roles of MAO A in promoting tumor metastasis, determined MAO A functions in PCa by defining its roles in reactive oxygen species production and augmentation of HIF1-mediated signaling, and developed a MHI clorgyline, a novel pharmacological inhibitor of MAO A for targeted therapy and noninvasive imaging of PCa. Throughout the Year 3, we investigated the effect of hypoxia on MAO A and found that hypoxia induces MAO A expression and activity. We assessed the tumor-targeting properties of NIR-clorgyline for PCa in vivo and demonstrated its tumor-specificity in mouse xenograft model through NIR near infrared imaging. We generated MAO APten double KO mice and showed that deletion of MAO A delays PCa development and facilitates an immunostimulatory environment in the Pten KO mouse model of prostate adenocarcinoma.