Bone Morphogenetic Protein-10 Suppresses the Growth and Aggressiveness of Prostate Cancer Cells Through a Smad Independent Pathway

Abstract

BMPs have been implicated in the development of bone metastasis in prostate cancer. We investigated the role of BMP-10 in prostate cancer and prostate cancer cells. BMP-10 expression was examined in human prostate tissue and prostate cancer cell lines. BMP-10 was experimentally over expressed in human prostate cancer cells. The influence of BMP-10 on the biological behavior of prostate cancer cells was then investigated in in vitro studies. BMP-10 expression was decreased or absent in prostate tumors, particularly in higher grade foci. Forced BMP-10 over expression in prostate cancer cells decreased in vitro growth, cell matrix adhesion, invasion and migration. Furthermore, BMP-10 induced apoptosis in prostate cancer cells through a Smad independent pathway, in which the 2 downstream candidates of BMP receptors XIAP (ILP) and ERK1/2 were activated. Interestingly the failure of BMP-10 to activate BMP receptor-II and the Smads in WT cells was due to the expression of BMP receptor-IB, which acted as a negative regulator of BMP receptor-II mediated Smad dependent signaling. BMP-10 inhibits the growth of prostate cancer cells due largely to induced apoptosis via Smad independent signaling in which XIAP and ERK1/2 are involved. BMP-10 can also prevent prostate cancer cell migration and invasiveness. This suggests that BMP-10 may function as a tumor suppressor and apoptosis regulator for prostate cancer.