15P - PLGF regulates crosstalk between non-small cell lung cancer cells and tumor-associated macrophages in cancer vascularization and growth

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Non-Small-Cell Lung Cancer, Metastatic
Lung and other Thoracic Tumours
Pathology/Molecular Biology
Presenter Wei Zhang
Citation Annals of Oncology (2017) 28 (suppl_2): ii1-ii5. 10.1093/annonc/mdx090
Authors W. Zhang, Y. Lou, B. Yan, Y. Zhao, S. Cui, L. Jiang, B. Han
  • Department Of Pulmonary, Shanghai Chest Hospital, 200030 - Shanghai/CN

Abstract

Background

The growth and invasion of non-small cell lung cancer (NSCLC) require assistance of tumor-associated vascularization, the underlying molecular mechanisms of which remain eluted. Recently, we reported that placental growth factor (PLGF) was expressed by NSCLC cells, and promoted the metastasis of NSCLC cells. Here, we showed that NSCLC cells produced and secreted PLGF to signal to tumor-associated macrophages (TAM) through the surface expression of the receptor for PLGF, Flt-1, on macrophages.

Methods

Ten week-old male NOD/SCID mice were used for transplantation of 107 AAV-transduced/labeled A549 cells by tail vein injection. Bones from 12-week-old male C57BL/6 mice were flushed with macrophage culture media. Isolated bone-marrow-derived macrophages (105) were co-cultured either with equal number of A549 cells (105) with/without of 10µmol/l SB431542, or with/without recombinant PLGF (100ng), or with/without of 10 µg/l sFlt-1. Two days after co-culture, the changes in A549 cell number were determined with an MTT assay, and the macrophage subtypes were determined by flow cytometry.

Results

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 transforming growth factor β 1 (TGFβ1) to enhance the growth of endothelial cells in a HUVEC assay.

Conclusions

Thus, our studies suggest that the cross-talk between TAM and NSCLC cells via PLGF/Flt-1 and TGFβ receptor signaling may promote the growth and vascularization of NSCLC.

Clinical trial identification

Legal entity responsible for the study

Shanghai Chest Hospital

Funding

This work was supported by the National Natural Science foundation of China (81402378).

Disclosure

All authors have declared no conflicts of interest.