Placental Growth Factor Mediates Crosstalk Between Lung Cancer Cells and Tumor-Associated Macrophages in Controlling Cancer Vascularization and Growth

Background/Aims: Assistance with tumor-associated vascularization is needed for the growth and invasion of non-small cell lung cancer (NSCLC). Recently, it was shown that placental growth factor (PLGF) expressed by NSCLC cells had a critical role in promoting the metastasis of NSCLC cells. However, the underlying molecular mechanisms remain elusive. Methods: Here, we first established a NSCLC model in mice that allows us not only to isolate tumor cells from non-tumor cells in the tumor, but also to trace tumor cells in living animals. Levels of PLGF, its unique receptor Flt-1, as well as transforming growth factor beta 1 (TGF beta 1) was examined in tumor cells and tumor-associated macrophages (TAM) by RT-qPCR. A transwell well coculture system and HUVEC assay were applied to study the crosstalk between NSCLC cells and TAM. Results: NSCLC cells produced and secreted PLGF to signal to tumor-associated macrophages (TAM) through surface expression of Flt-1 on macrophages. In a transwell coculture system, PLGF secreted by NSCLC cells triggered macrophage polarization to a TAM subtype that promote growth of NSCLC cells. Moreover, polarized TAM seemed to secrete TGF beta 1 to enhance the growth of endothelial cells in a HUVEC assay. Conclusion: The crosstalk between TAM and NSCLC cells via PLGF/Flt-1 and TGF beta receptor signaling may promote the growth and vascularization of NSCLC. (C) 2018 The Author(s) Published by S. Karger AG, Basel