Research Paper Volume 16, Issue 18 pp 12498—12509
SHP2 mediates STAT3/STAT6 signaling pathway in TAM to inhibit proliferation and metastasis of lung adenocarcinoma
- 1 Clinical Laboratory, Hebei General Hospital, Shijiazhuang 050051, Hebei, China
- 2 Hebei Clinical Research Center for Laboratory Medicine, Shijiazhuang 050051, Hebei, China
- 3 Hebei Key Laboratory of Molecular Medicine, Shijiazhuang 050051, Hebei, China
Received: May 1, 2023 Accepted: March 25, 2024 Published: May 14, 2024
https://doi.org/10.18632/aging.205799How to Cite
Copyright: © 2024 Chai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: This study examines SHP2’s influence on the STAT3/STAT6 pathway in tumor-associated macrophages (TAMs) and its impact on lung adenocarcinoma proliferation and metastasis.
Methods: Lung cancer A549 and NCI-H1688 cell lines were subcutaneously injected into nude mice. Macrophages were isolated using flow cytometry and analyzed for CD163, CD206, and Arginase-1 levels via western blot. Similarly, the effect on THP1 cell-associated proteins was assessed. The impact on A549 and NCI-H1688 cell migration, invasion, and proliferation was evaluated through wound healing, Transwell assays, and CCK8.
Results: Compared to controls, the sh-RNA SHP2 group showed increased tumor volume and higher expression levels of CD163, CD206, Arginase-1, p-STAT3, p-STAT6, IL-4, IL-10, and various cathepsins in macrophages and THP1 cells. However, p-STAT1 and p-STAT5 levels remained unchanged. The sh-RNA SHP2 group also demonstrated enhanced migration, invasion, and proliferation in both cell lines.
Conclusions: SHP2 negatively affects the STAT3/STAT6 pathway in TAMs, promoting M2 polarization and cathepsin secretion, which enhances lung adenocarcinoma cell proliferation and metastasis.