Targeting Discoidin Domain Receptors in Prostate Cancer
Technical Report,01 Aug 2018,31 Jul 2019
Wayne State University Detroit United States
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We report the progress of our studies focusing on the Discoidin Domain Receptors DDRs, a set of kinase receptors that signal in response to collagen in prostate cancer PCa. The projects goal was to define the expression and therapeutic potential of DDRs in prostate cancer. We conducted a comprehensive analyses of DDR1 expression in a 200 case GradeStage tissue microarray TMA with clinical data, using a highly specific anti-DDR1 antibody. Comparing low 734 and high734 Gleason Score GS tumors, we found that PCa malignant progression is associated with reduced expression of DDR1in the plasma membrane of tumor cells of high GS tumors. However, no significant associations between DDR1 expression and overall survival or biochemical recurrence were found. A selective DDR1 neutralizing antibody blocked collagen-mediatedDDR1 activation in cultured PC3 cells. However, it had no impact on intraosseous tumor growth or bone response. However, target inhibition could not be determined. Downregulation of endogenous DDR1 in PC3 cells enhanced growth within bone,suggesting a tumor suppressive effect of DDR1. However, this effect was not conclusive. Studies on DDR1 function and subcellular distribution in culture cells is ongoing. Overall, our studies suggest a complex role of DDR1 in PCa progression that need to be further evaluated.
- Medicine and Medical Research