The crosstalk between lung cancer cells and platelets promotes tumor angiogenesis in vivo and in vitro

Purpose We previously showed that the crosstalk of H1975 cells and platelets (PLTs) may promote tumor angiogenesis. This study aimed to determine whether other lung cell lines (LC) interacting with PLTs could affect tumor angiogenesis through in vivo and in vitro experiments. Methods Cell Counting Kit-8, EdU cell proliferation, wound healing, Transwell invasion, F-actin staining, tube formation, ELISA and western blot assays were performed to investigate the properties and the expression levels of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), p-VEGFR2, PI3K, p-PI3K, Akt, p-Akt and eNOS in supernatants or HUVECs. Then, using mouse models, immunohistochemistry was applied to detect the expression levels of CD31 and VEGF. Results Compared with single-cultured HUVECs (EC) or incubation with either LC supernatant (EC + LC) or activated PLT supernatant (EC + PLT), incubation with SN_LCP (supernatant derived from LC cocultured with PLT, named the EC + LC + PLT group) improved the viability, proliferation, migration, invasion, and tube formation activities of HUVECs and the expression of F-actin, VEGF, VEGFR2, p-VEGFR2, p-PI3K, p-Akt and eNOS in HUVECs. Higher expression levels of CD31 and VEGF were found in the LLC + PLT (mouse model inoculated with Lewis lung cancer (LLC) cells cocultured with PLTs) group than in the LLC (mouse model inoculated with LLC cells alone) group. However, the increased angiogenic properties of HUVECs were inhibited by apatinib, an inhibitor of VEGFR2. Conclusion Lung carcinoma cells interacting with PLTs may play a key role in lung carcinoma angiogenesis through the VEGF/VEGFR2 signaling pathway.

Automated summary

This study aimed to investigate whether the interaction between lung cell lines and platelets (PLTs) could affect tumor angiogenesis. The results showed that co-culturing lung cell lines with PLTs enhanced the proliferation, migration, invasion, and tube formation activities of endothelial cells. Similar results were observed in a mouse model. The study also found that the VEGF/VEGFR2 signaling pathway played a key role in lung carcinoma angiogenesis.