Platelets promote osteosarcoma cell growth through activation of the platelet-derived growth factor receptor-Akt signaling axis.
Bottom Line: The addition of supernatants of osteosarcoma-platelet reactants also increased the growth of MG63 and HOS cells as well as the level of phosphorylated-PDGFR and -Akt.Sunitinib or LY294002, but not erlotinib, significantly inhibited the platelet-induced proliferation of osteosarcoma cells, indicating that PDGF released from platelets plays an important role in the proliferation of osteosarcomas by activating the PDGFR and then Akt.Our results suggest that inhibitors that specifically target osteosarcoma-platelet interactions may eradicate osteosarcomas.
Affiliation: Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.Show MeSH
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Mentions: Activation of PDGFRα and PDGFRβ is mediated by PDGFs, and only PDGF-BB can activate both PDGFRs. To determine whether PDGF-BB was released during the osteosarcoma cell-mediated platelet aggregation, we measured the amount of PDGF-BB in the supernatants of the osteosarcoma-platelet reactants using an enzyme linked immunosorbent assay (ELISA). The level of PDGF-BB was increased in supernatants of osteosarcoma-platelet aggregates compared with platelets alone (Fig. 3a). To assess the contribution of PDGFs to the activation of PDGFR-Akt axis, we treated MG63/ZsGreen and HOS/ZsGreen cells with the supernatant of the osteosarcoma-platelet reactant in the absence or presence of PDGFRs inhibitor, sunitinib. We found that the levels of phospho-PDGFRβ and phospho-Akt increased in osteosarcoma cell lines in the absence of, but not in the presence of sunitinib (Figs 3b,c). These results indicate that PDGFs released from activated platelets by the initiation of osteosarcoma-platelet interactions activated the PDGFR-Akt signaling axis.
Affiliation: Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.