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Repulsive guidance molecule (RGM) family members RGMA, RGMB and RGMC areGPI-linked membrane proteins recently identified as co-receptor of bone morphogeneticproteins (BMPs). BMPs are a group of proteins enriched in bone and play importantroles in prostate cancer. The current study aimed to investigate roles playedby RGMs in prostate cancer. Expression of RGMs was examined in prostate cancercell lines and prostate cancer tissues using RT-PCR and immunohistochemical staining.Knockdown of each RGM in prostate cancer cells was performed using the respectiveanti-RGMA, RGMB and RGMC transgenes. A variety of in vitro function tests wereemployed to analyze the influence on cancer cell functions by RGM knockdown. Theimplications of RGM knockdown in BMP signalling were also examined using bothWestern blot and real-time quantitative PCR. Knockdown of RGMA had no effect oncell growth, migration and invasion, but promoted cell-matrix adhesion. Knockdownof RGMB and RGMC increased growth and adhesion, but only RGMB knockdown increasedcapacities of migration and invasion in PC-3 cells. Further investigations showedan increase in Smad-3 activation and reduced levels of Smad-1 in PC-3 cells byRGMB and RGMC knockdown, and also an up-regulation of ID1, a BMP target gene particularlyin exposure to BMP7. RGMs play inhibitory roles in prostate cancer by suppressingcell growth, adhesion, migration and invasion. RGMs can coordinate Smad-dependentsignalling of BMPs in prostate cancer cells.

international journal of oncology

Repulsive guidance molecules, novel bone morphogenetic protein co-receptors, are key regulators of the growth and aggressiveness of prostate cancer cells