PIGF and Flt-1 on the surface of macrophages induces the production of TGF-β1 by polarized tumor-associated macrophages to promote lung cancer angiogenesis

Background: The interaction between tumor cells and tumor microenvironment is a necessary condition for promoting the metastasis of malignant tumors. Methods: Two different transwell culture systems were interfered with by recombinant factor placental growth factor (re-PIGF) and the re-PIGF + transforming growth factor-beta 1 (TGF-beta 1)-neutralizing antibody (anti-TGF-beta 1). We performed immunofluorescence, flow cytometry and enzyme linked immunosorbent assay (ELISA) to analyze the expression of PIGF, fms-like tyrosine kinase-1 (Flt-1), macrophage marker F4/80(+), macrophage M2 marker CD163(+) and TGF-beta 1 in vitro. Meanwhile, cell viability assay and optical microscope assay were conducted to explore the cell viability and vascularization ability of human umbilical vein endothelial cells (HUVECs). Results: Re-PIGF increased the expression of PIGF in A549 cells and the expression of Flt-1 in BM-Mac cells, and significantly enhanced the ability of bone marrow-derived macrophages (BM-Mac) to transform into macrophages. At the same time, re-PIGF increased the expression of cytokine TGF-beta 1 in A549 cells/BM-Mac transwell culture system. On the contrary, re-PIGF + anti-TGF-beta 1 inhibited the expression of Flt-1 in BM-Mac cells and inhibited the ability of BM-Mac cells to transform into macrophages. Finally, re-PIGF + anti-TGF-beta 1 reduced the cell viability and angiogenesis of HUVECs. Conclusion: The surface molecule PIGF of lung cancer cells could bind to the receptor Flt-1 on the surface of macrophages, thereby increasing the production of TGF-beta 1, and ultimately promoting the formation of angiogenesis in lung cancer.