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Platelets promote osteosarcoma cell growth through activation of the platelet-derived growth factor receptor-Akt signaling axis.

Takagi S, Takemoto A, Takami M, Oh-Hara T, Fujita N - Cancer Sci. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.

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Involvement of the platelet-derived growth factor receptor (PDGFR) -Akt signaling axis in the platelet-induced growth of osteosarcoma cells. (a, b) MG63/ZsGreen (a) or HOS/ZsGreen (b) cells in 24-well were co-cultured with platelets (2 × 107 in Tyrode's buffer containing 200 μM CaCl2) in the presence of DMSO, the epidermal growth factor receptor (EGFR) inhibitor erlotinib (1 μM), the PDGFR inhibitor sunitinib (1 μM), or the PI3K inhibitor LY294002 (20 μM). After a 48-h incubation, cells were lysed and the fluorescence of ZsGreen was measured to determine relative cell growth. The error bars indicate the mean ± SD of triplicate experiments. **P < 0.01 and *P < 0.05 (Student's t-test). NS, not significant.
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fig04: Involvement of the platelet-derived growth factor receptor (PDGFR) -Akt signaling axis in the platelet-induced growth of osteosarcoma cells. (a, b) MG63/ZsGreen (a) or HOS/ZsGreen (b) cells in 24-well were co-cultured with platelets (2 × 107 in Tyrode's buffer containing 200 μM CaCl2) in the presence of DMSO, the epidermal growth factor receptor (EGFR) inhibitor erlotinib (1 μM), the PDGFR inhibitor sunitinib (1 μM), or the PI3K inhibitor LY294002 (20 μM). After a 48-h incubation, cells were lysed and the fluorescence of ZsGreen was measured to determine relative cell growth. The error bars indicate the mean ± SD of triplicate experiments. **P < 0.01 and *P < 0.05 (Student's t-test). NS, not significant.

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.


Platelets promote osteosarcoma cell growth through activation of the platelet-derived growth factor receptor-Akt signaling axis.

Takagi S, Takemoto A, Takami M, Oh-Hara T, Fujita N - Cancer Sci. (2014)

Involvement of the platelet-derived growth factor receptor (PDGFR) -Akt signaling axis in the platelet-induced growth of osteosarcoma cells. (a, b) MG63/ZsGreen (a) or HOS/ZsGreen (b) cells in 24-well were co-cultured with platelets (2 × 107 in Tyrode's buffer containing 200 μM CaCl2) in the presence of DMSO, the epidermal growth factor receptor (EGFR) inhibitor erlotinib (1 μM), the PDGFR inhibitor sunitinib (1 μM), or the PI3K inhibitor LY294002 (20 μM). After a 48-h incubation, cells were lysed and the fluorescence of ZsGreen was measured to determine relative cell growth. The error bars indicate the mean ± SD of triplicate experiments. **P < 0.01 and *P < 0.05 (Student's t-test). NS, not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4317862&req=5

fig04: Involvement of the platelet-derived growth factor receptor (PDGFR) -Akt signaling axis in the platelet-induced growth of osteosarcoma cells. (a, b) MG63/ZsGreen (a) or HOS/ZsGreen (b) cells in 24-well were co-cultured with platelets (2 × 107 in Tyrode's buffer containing 200 μM CaCl2) in the presence of DMSO, the epidermal growth factor receptor (EGFR) inhibitor erlotinib (1 μM), the PDGFR inhibitor sunitinib (1 μM), or the PI3K inhibitor LY294002 (20 μM). After a 48-h incubation, cells were lysed and the fluorescence of ZsGreen was measured to determine relative cell growth. The error bars indicate the mean ± SD of triplicate experiments. **P < 0.01 and *P < 0.05 (Student's t-test). NS, not significant.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus