Human Bone Marrow Activates the Akt Pathway in Metastatic Prostate Cells through Transactivation of the α-Platelet–Derived Growth Factor Receptor

摘要: The factors regulating the bone tropism of disseminated prostate cancer cells are still vaguely defined. We report that metastasize to skeleton respond human marrow with a robust stimulation phosphatidylinositol 3-kinase/Akt pathway, whereas lack bone-metastatic potential negligibly. majority this Akt activation is dependent on α-platelet–derived growth factor receptor (α-PDGFR) signaling, which was shown using small-molecule inhibitor PDGFR signaling AG1296. Low concentrations PDGF-AA and PDGF-BB found in aspirates, were detected by ELISA, do not account for high levels α-PDGFR signaling. Additionally, neutralizing PDGF binding α-PDGFR–specific antibody (IMC-3G3) failed produce significant inhibition marrow–induced activation. However, inhibitory effect IMC-3G3 rivaled AG1296 when incubation done under conditions stimulated internalization. conclude activated multiple soluble contained within marrow, addition its natural ligands, transactivation localization plasma membrane. Therefore, expression may provide select phenotypes advantage microenvironment. [Cancer Res 2007;67(2):555–62]