ELANE Promotes M2 Macrophage Polarization by Down-Regulating PTEN and Participates in the Lung Cancer Progression

ABSTRACT

Background

Macrophages are one of the most important immunoinflammatory cell populations in the tumor microenvironment (TME). In this study, we preliminarily investigated the upstream pathway of M2 macrophage polarization affecting lung cancer progression.

Methods

Bioinformatics analysis was used to evaluate genes closely associated with lung adenocarcinoma and their relationship with immune cells. THP-1 monocytes were induced into M2 macrophages. The expression of markers in M2 macrophages was detected by quantitative reverse transcription-PCR (qRT-PCR), enzyme linked immunosorbent assay (ELISA), and flow cytometry. The effects of neutrophil elastase (ELANE)-mediated M2 macrophages on lung cancer cell proliferation, migration and invasion and tumor growth were investigated by in vitro and in vivo experiments after co-culture of macrophage conditioned medium (CM) and lung cancer cell lines A549 and H1299. The PTEN protein expression was detected by Western blotting.

Results

ELANE was significantly positively correlated with M2 macrophages. ELANE up-regulated the expression of the M2 macrophage markers CD206, CCL22, IL-10 and CCL18 and increased the proportion of CD206+ macrophages. Compared with M0-CM, M2-CM promoted cell proliferation, migration, and invasion, and (M2+ELANE)-CM further enhanced this effect. In vivo, ELANE promoted M2 macrophage-induced tumor growth in lung cancer mice model. In vitro experiments showed that ELANE can down-regulate the expression of PTEN and promote the polarization of M2 macrophages.

Conclusion

ELANE promotes the polarization of M2 macrophages by down-regulating PTEN, thus promoting cell proliferation, migration, and invasion in vitro and growth of lung cancer cells in vivo.

KEYWORDS:

• ELANE
• lung cancer
• M2 macrophages
• PTEN

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/08820139.2022.2115379

Additional information

Funding

This work was supported by a grant from the Joint Special Fund for Applied Basic Research Programs of Kunming Medical University (No. 202001AY070001-025).