Bone morphogenetic protein-10 suppresses the growth and aggressiveness of prostate cancer cells through a Smad independent pathway.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ye
Lin
L
Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, United Kingdom. yel@cf.ac.uk
Kynaston
Howard
H
Jiang
Wen G
WG
D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000502:physiology*; D049109:Cell Proliferation; D006801:Humans; D008297:Male; D011467:Prostate / Q000166:cytology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D051785:Smad Proteins / Q000502:physiology*; D014407:Tumor Cells, Cultured
C541386:BMP10 protein, human; D019485:Bone Morphogenetic Proteins; D051785:Smad Proteins