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Cell Physiol Biochem. 2018;47(6):2534-2543. doi: 10.1159/000491650. Epub 2018 Jul 10.

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

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Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China.



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.


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 β1 (TGFβ1) was examined in tumor cells and tumor-associated macrophages (TAM) by RT-qPCR. A transwell well co-culture system and HUVEC assay were applied to study the crosstalk between NSCLC cells and TAM.


NSCLC cells produced and secreted PLGF to signal to tumor-associated macrophages (TAM) through surface expression of Flt-1 on macrophages. In a transwell co-culture 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 TGFβ1 to enhance the growth of endothelial cells in a HUVEC assay.


The cross-talk between TAM and NSCLC cells via PLGF/Flt-1 and TGFβ receptor signaling may promote the growth and vascularization of NSCLC.


Non-small cell lung cancer (NSCLC); Placental growth factor (PLGF); Transforming growth factor β1 (TGFβ1); Tumor-associated macrophages (TAM)

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