Tumor-associated Macrophages Mediate Gefitinib Resistance in Lung Cancer through HGF/c-met Signaling Pathway


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Abstract

Background::The biological behavior of cells changes after they develop drug resistance, and the degree of resistance will be affected by the tumor microenvironment. In this study, we aimed to study the effects of M2 macrophages on gefitinib resistance.

Methods:We polarized THP-1 cells into M0 and M2 macrophages, and conducted various experiments to investigate the effects of M2 macrophages on gefitinib resistance in lung cancer.

Results:We found that M2 macrophages promote gefitinib resistance in HCC827 and PC9 cells. In addition, we used ELISA to measure the secretion level of HGF. HGF secretion levels were significantly increased in M2 macrophages. Exogenous HGF remarkably increased the proliferation and invasion in HCC827 and PC9 cells. However, the addition of anti-HGF antibodies abolished the proliferation and invasion of both HCC827 and PC9 cells promoted by M2 macrophages. Furthermore, M2 macrophages or exogenous HGF significantly increased the expression of p-met and p-ERK in HCC827 and PC9 cells, while anti-HGF antibodies diminished the expression of p-met and p-ERK by neutralizing HGF in M2 macrophages.

Conclusion::Our results revealed that M2 macrophages promote gefitinib resistance by activating ERK and HGF/c-met signaling pathways in HCC827 and PC9 cells. Our findings provide a new therapeutic strategy for gefitinib resistance in lung cancer.

About the authors

Xiali Tang

Pulmonary and Critical Care Medicine, The 903rd Hospital of PLA

Email: info@benthamscience.net

Yu Chen

Pulmonary and Critical Care Medicine, The 903rd Hospital of PLA

Email: info@benthamscience.net

Demin Jiao

Pulmonary and Critical Care Medicine, The 903rd Hospital of PLA

Email: info@benthamscience.net

Xiang Liu

Pulmonary and Critical Care Medicine, The 903rd Hospital of PLA

Email: info@benthamscience.net

Jun Chen

Pulmonary and Critical Care Medicine, The 903rd Hospital of PLA

Email: info@benthamscience.net

Yongyang Liu

School of the 1st Clinical Medical Sciences, Wenzhou Medical University

Email: info@benthamscience.net

Chunyan Jiang

Pulmonary and Critical Care Medicine, The 903rd Hospital of PLA

Author for correspondence.
Email: info@benthamscience.net

Qingyong Chen

Pulmonary and Critical Care Medicine, The 903rd Hospital of PLA

Author for correspondence.
Email: info@benthamscience.net

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