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

Xiali      Tang; Yu      Chen; Demin      Jiao; Xiang      Liu; Jun      Chen; Yongyang      Liu; Chunyan      Jiang; Qingyong      Chen

doi:10.2174/0118715206261966231103043418

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.

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Graphical Abstract

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DOI https://dx.doi.org/10.2174/0118715206261966231103043418	Print ISSN 1871-5206
Publisher Name Bentham Science Publisher	Online ISSN 1875-5992

Anti-Cancer Agents in Medicinal Chemistry

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

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