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

• Main Authors: Changjun He, Kaibin Zhu, Xue Bai, Yingbin Li, Dawei Sun, Yaoguo Lang, Jinfeng Ning, Fenglin Sun, Changfa Qu, Shidong Xu
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2018-07-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Placental growth factor (PLGF); Non-small cell lung cancer (NSCLC); Tumor-associated macrophages (TAM); Transforming growth factor β1 (TGFβ1)
• Online Access: https://www.karger.com/Article/FullText/491650
• ISSN: 1015-8987; 1421-9778

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