biostudies-literatureHuang WNCI NIH HHS4527-35https://www.ebi.ac.uk/biostudies/studies/S-EPMC3482867biostudies-literatureUnknown31(42)Although increasing evidence suggests a critical role for platelet-derived growth factor (PDGF) receptor β (β-PDGFR) signaling in prostate cancer (PCa) progression, the precise roles of β-PDGFR and PDGF isoform-specific cell signaling have not been delineated. Recently, we identified the PDGF-D isoform as a ligand for β-PDGFR in PCa and showed that PDGF-D is activated by serine protease-mediated proteolytic removal of the CUB domain in a two-step process, yielding first a hemidimer (HD) and then a growth factor domain dimer. Herein, we demonstrate that the expression of PDGF-D in human PCa LNCaP cells leads to enhanced bone tumor growth and bone responses in immunodeficient mice. Histopathological analyses of bone tumors generated by PDGF-D-expressing LNCaP cells (LNCaP-PDGF-D) revealed osOncogeneA novel function for platelet-derived growth factor D: induction of osteoclastic differentiation for intraosseous tumor growth.PMC3482867CA123362CA64139R01 CA064139R01 CA123362T32-CA009531R29 CA064139R01 CA137280T32 CA009531R01CA137280Fridman YSaliganan ACher MLWiesner CHuang WBonfil RDUstach CVKim HRConley-LaComb MKfalseA novel function for platelet-derived growth factor D: induction of osteoclastic differentiation for intraosseous tumor growth.Although increasing evidence suggests a critical role for platelet-derived growth factor (PDGF) receptor β (β-PDGFR) signaling in prostate cancer (PCa) progression, the precise roles of β-PDGFR and PDGF isoform-specific cell signaling have not been delineated. Recently, we identified the PDGF-D isoform as a ligand for β-PDGFR in PCa and showed that PDGF-D is activated by serine protease-mediated proteolytic removal of the CUB domain in a two-step process, yielding first a hemidimer (HD) and then a growth factor domain dimer. Herein, we demonstrate that the expression of PDGF-D in human PCa LNCaP cells leads to enhanced bone tumor growth and bone responses in immunodeficient mice. Histopathological analyses of bone tumors generated by PDGF-D-expressing LNCaP cells (LNCaP-PDGF-D) revealed os2012-01-01T00:00:00Z2012 Oct2025-07-06T03:05:45.696Z2025-07-06T03:05:45.696ZS-EPMC34828672215804310.1038/onc.2011.573