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: Osteosarcomas form pulmonary metastasis by inducing platelet aggregation.(16,17) To assess the role of osteosarcoma-platelet interactions in determining the malignant phenotype of osteosarcomas, we first measured the abilities of the human osteosarcoma cell lines MG63 and HOS to induce platelet aggregation. We found that each osteosarcoma cell line induced platelet aggregation to an extent that is consistent with published studies (Fig. 1a). We next examined the influence of platelets on the growth of the osteosarcoma cell lines. Because of the high concentration of adenosine triphosphate (ATP) in platelets, we were unable to determine the growth of osteosarcoma cells using proliferation assays that measure ATP. Therefore, we generated stable transfectants of MG63 and HOS cells that expressed ZsGreen (MG63/ZsGreen and HOS/ZsGreen, respectively) and measured ZsGreen fluorescence to determine the number of viable cells. Although the growth rates of MG63/ZsGreen and HOS/ZsGreen cells were slow in the presence of 0.5% FBS, the growth rate of each cell line was significantly enhanced in proportion to the number of washed platelets added to the cultured cells (Fig. 1b). We found that the addition of the supernatant of an osteosarcoma-platelet reactant, but not that of the PBS-platelet reactant, significantly enhanced the growth of MG63/ZsGreen and HOS/ZsGreen cells (Fig. 1c). These results indicate that the proliferation of osteosarcoma cells is increased in the presence of platelets as well as by supernatants of osteosarcoma-platelet reactant.
Affiliation: Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.