1. Academic Validation
  2. MCP-1/CCL2 Mediated by Autocrine Loop of PDGF-BB Promotes Invasion of Lung Cancer Cell by Recruitment of Macrophages Via CCL2-CCR2 Axis

MCP-1/CCL2 Mediated by Autocrine Loop of PDGF-BB Promotes Invasion of Lung Cancer Cell by Recruitment of Macrophages Via CCL2-CCR2 Axis

  • J Interferon Cytokine Res. 2019 Apr;39(4):224-232. doi: 10.1089/jir.2018.0113.
Mei Ding 1 Shao-Jun He 1 Jiong Yang 1
Affiliations

Affiliation

  • 1 Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, P. R. China.
Abstract

Platelet-derived growth factor-BB (PDGF-BB) is recognized as a potential player in a paracrine manner in tumor stroma development. PDGF-BB has an autocrine growth function in lung Cancer cells; however, the mechanism in nonsmall-cell lung Cancer is not fully understood. In this study, we report that PDGF-BB increased monocyte chemoattractant protein-1 (MCP-1)-dependent macrophage recruitment and that expression of metastatic genes increased in A549 cells cocultured with RAW 264.7 macrophages. Similar to exogenous PDGF-BB, PDGF-BB might have a self-stimulation in invasion of Cancer cells during reciprocal activation of Cancer cells and tumor-associated macrophages through secretion of soluble proteins. Also, we found that PDGF-BB upregulates both mRNA and protein level of MCP-1 expression in human A549 cells through mitogen-activated protein kinases and phosphatidylinositol 3-kinase/Akt cell signaling pathways, binding NFκB to MCP-1 promoter site and PDGF-Rβ as critical receptor. These results suggested that MCP-1/chemokine (C-C motif) ligand 2 (CCL2) expression mediated by the autocrine loop of PDGF-BB enhanced recruitment of macrophages through CCL2-CCR2 axis, which could ultimately increase expression of metastatic genes in lung Cancer cells, finally promoting invasive potential of Cancer cells.

Keywords

MCP-1 (CCL2); PDGF-BB; invasion; lung cancer; macrophages.

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