Cross-talk between endothelial and tumor cells via basic fibroblast growth factor and vascular endothelial growth factor signaling promotes lung cancer growth and angiogenesis

The present study aimed to investigate the origin and potential mechanisms of angiogenesis in lung cancer cells. Normal endothelial cells (ECs) were isolated from human umbilical vein ECs (HUVECs) and cultured. The human lung cancer A549 cell line was also used. The cross-talk model between the HUVECs and the A549 cell line was constructed in vitro using a Millicell co-culture system. Cluster of differentiation (CD)31 and CD146 were selected as markers of the HUVECs. CD105 was used as a marker of activated blood vessel ECs in the tumor microenvironment and glucose-regulated protein-78 (GRP-78) was used as a biomarker of the A549 cells. The four markers were detected by immunofluorescence, and the mean optical density was calculated. The growth curves were constructed using the cell proliferation reagent, WST-1. The expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the media was measured using an ELISA. The average proliferation rates of the co-cultured HUVECs and A549 cells were significantly higher than those observed in the control groups. The fluorescence intensity of CD105 expression in the co-cultured HUVECs was higher than that in the control group. The fluorescence intensity of GRP-78 in the co-cultured A549 cells was higher than that in the A549 cells cultured alone. The average expression levels of VEGF and bFGF in the co-cultured model were higher than in the control groups. Therefore, it was hypothesized that cancer cells may induce the differentiation of normal ECs into vascular ECs via the secretion of VEGF and bFGF. Furthermore, vascular ECs can affect the proliferation and differentiation of cancer cells.