Targeting Discoidin Domain Receptors in Prostate Cancer
Technical Report,01 Aug 2015,31 Jul 2016
Wayne State University Detroit United States
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We report our major findings on our studies focusing on the Discoidin Domain Receptors DDRs, a set of kinase receptors that signal in response to collagen. The projects goal is to define the expression and therapeutic potential of DDRs in prostate cancer. During the first funding period, we conducted immunohistochemical studies by staining a 200 case GradeStage tissue microarray TMA that was examined for DDR1 expression using a highly specific antibody. This TMA includes 1600cores that are being evaluated for antigen expressionlocalization and association with Gleason score. These studies are ongoing. We examined the anti-tumor effect of a highly specific DDR1 blocking antibody in a mouse model of intraosseous tumor growth using the PC3 human prostate cancer cell line. We obtained a humanized anti-DDR1 antibody, which blocks receptor activation by collagen I. Mice were inoculated with PC3 cells and anti-DDR1 or control antibody treatment. The study showed an apparent reduced tumor burden in the treated mice using bioluminescence. However, several mice suffered bone fractures, which compromised analyses of intraosseous tumor growth by bone histomorphometry, and thus these studies were inconclusive. We are currently fine-tuning the experimental conditions to prevent excessive intraosseous tumor growth by testing different cell inoculums.