Discoidin Domain Receptor 2 (DDR2) Promotes Prostate Cancer Progression in Cooperation with Collagen Remodeling.

Abstract

Prostate cancer is one of the most common malignancies in men and remodeling of extracellular collagen, especially collagen type I immensely contributes to the progress of prostate cancer. Discoidin domain receptor 2 (DDR2) is a receptor of collagen type I and transmits intracellular signaling in not only normal cells but also malignant cells, facilitating tumor progression. However, clinical and biological significance of DDR2 has not been well examined in prostate cancer. We therefore immunolocalized DDR2 and collagen type I in 117 prostate carcinoma tissues and correlated their immunoreactivity with clinicopathological characteristics of prostate cancer. We also conducted in vitro experiments using human prostate cancer cell lines to confirm the findings from immunohistochemical study. DDR2 immunoreactivity was positively associated with an aggressive phenotype of prostate cancer, partially in association with dense collagen I tissues which consisted of thin fibers. In addition, DDR2 immunoreactivity was significantly correlated with adverse clinical outcomes of prostate cancer. In vitro experiments revealed that DDR2 promoted proliferation and migration of PC-3 and DU-145 prostate cancer cell lines. It is therefore speculated that DDR2 promoted prostate cancer progression by interacting with collagen I, serving as a potent prognostic factor in prostate cancer.