Open AccessPlatelets promote osteosarcoma cell growth through activation of the platelet‐derived growth factor receptor‐Akt signaling axis
Author(s) -
Takagi Satoshi,
Takemoto Ai,
Takami Miho,
Ohhara Tomoko,
Fujita Naoya
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12464
Subject(s) - osteosarcoma , platelet , platelet derived growth factor , platelet derived growth factor receptor , cancer research , growth factor , cell growth , growth factor receptor , protein kinase b , cell culture , biology , chemistry , immunology , microbiology and biotechnology , receptor , phosphorylation , signal transduction , medicine , biochemistry , genetics
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 MG 63 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 MG 63 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 MG 63 and HOS cells as well as the level of phosphorylated‐ PDGFR and ‐Akt. Sunitinib or LY 294002, 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.