Reduced Expression of Discoidin Domain Receptor 1 (DDR1) is Associated with High Gleason Score and Bone Metastasis in Prostate Cancer

Discoidin Domain Receptors (DDRs) play a key role in mediating the cross talk between tumor cells and the stromal collagen matrix. Herein, we studied the contribution of DDR1 to aggressiveness in prostate cancer (PCa). First, we investigated the role of DDR1 in intraosseous growth using PC3 human PCa cells engineered to express short hairpin RNAs (shRNAs) against DDR1 or scrambled shRNA (control), which were then injected intratibially in male SCID mice. Histomorphometrical studies revealed that DDR1 downregulation resulted in a significant increase in intraosseous tumor growth when compared to control PC3 cells (PPP=0.002, Fisher’s exact test). Collectively, these data highlight an unreported role of DDR1 in PCa whereby reduced DDR1 expression in the membrane compartment is associated with a more aggressive disease.