title: Platelets promote osteosarcoma cell growth through activation of the platelet-derived growth factor receptor-Akt signaling axis.
abstract: The interactions of tumor cells with platelets contribute to the progression of tumor malignancy, and the expression levels of platelet aggregation-inducing factors positively correlate with the metastatic potential of osteosarcoma cells. However, it is unclear how tumor-platelet interaction contributes to the proliferation of osteosarcomas. We report here that osteosarcoma-platelet interactions induce the release of platelet-derived growth factor (PDGF) from platelets, which promotes the proliferation of osteosarcomas. Co-culture of platelets with MG63 or HOS osteosarcoma cells, which could induce platelet aggregation, enhanced the proliferation of each cell line in vitro. Analysis of phospho-antibody arrays revealed that co-culture of MG63 cells with platelets induced the phosphorylation of platelet derived growth factor receptor (PDGFR) and Akt. 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.
authors: Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors: Satoshi
authors: S
authors: Takagi
authors: Ai
authors: A
authors: Takemoto
authors: Miho
authors: M
authors: Takami
authors: Tomoko
authors: T
authors: Oh-Hara
authors: Naoya
authors: N
authors: Fujita
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D001859:Bone Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D012516:Osteosarcoma / Q000378:metabolism*; D010974:Platelet Aggregation / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017479:Receptors, Platelet-Derived Growth Factor; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; osteosarcoma; platelet aggregation; platelet derived growth factor receptor; tumor-platelet interaction