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: To assess the role of the activation of the PDGFR-Akt axis in the growth of MG63 cells, we determined the effects of sunitinib, LY294002, or erlotinib, which inhibit the activity of the PDGFRs, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), or EGFR, respectively. Sunitinib and LY294002, but not erlotinib, inhibited the growth of MG63 and HOS cells when they were co-cultured with platelets (Figs 4a,b). These results indicate that activation of the PDGFR-Akt axis contributes to the platelet-dependent proliferation of osteosarcoma cells.
Affiliation: Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.