MSR1 Deficiency Inhibits the Progression of Non-Small Cell Lung Cancer by Restraining M2 Macrophage Polarization

Abstract

Background: Alternatively activated type 2 (M2) macrophage significantly regulates multiple stages of malignant progression, including cancer cell proliferation, drug resistance and immunosuppression. The role of many key receptors including macrophage scavenger receptor 1 (MSR1) in the macrophage polarization process is unclear. This study assessed the effect of MSR1 on M2 type polarization of macrophage and malignant state in lung cancer cells. Methods: The M0 macrophage model was constructed with the human monocytic leukemia cells (THP-1) treated with Phorbol-12-myristate-13-acetate (PMA). The M2 polarization of macrophages was obtained through M0 macrophages treated with interleukin-4 (IL-4) and IL-13. MSR1 knockdown macrophage model was established. MSR1 expression was identified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence assays in macrophages. The key genes cluster of differentiation 206 (CD206), CD163 and C-C motif chemokine ligand 22 (CCL22) in macrophages were determined by RT-qPCR assay in macrophages. The key proteins CD68 and CD163 in macrophages were determined by immunofluorescence assay. Enzyme linked immunosorbent assay (ELISA) was also used to test IL-10 and CCL18 levels in the macrophage culture. Cisplatin sensitivity tests were performed on A549 and H1975 cells treated with gradient drug dose (0, 1, 2, 4, 8, 16 μM cisplatin). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation and transwell assays were used to verify proliferation and migration activity of A549 and H1975 cells in vitro. Results: MSR1 levels in M2 macrophage were significantly higher than in M0 macrophage (p < 0.05). Decreased MSR1 expression could restrain M2 macrophage polarization (p < 0.05). Mechanistic research determined that MSR1 deficient M2 macrophages could inhibit the abilities to proliferate and metastasize of H1975 and A549 cells (p < 0.05). Notably, the absence of MSR1 in M2 macrophages significantly reversed the cisplatin sensitivity of cancer cells. Conclusions: Our experiments have identified a novel mechanism of M2 type polarization of macrophage during the development of lung cancer. MSR1 can be a potential immunotherapeutic target.