SHP2 介导 TAM 中的 STAT3/STAT6 信号通路抑制肺腺癌的增殖和转移。

SHP2 mediates STAT3/STAT6 signaling pathway in TAM to inhibit proliferation and metastasis of lung adenocarcinoma.

机构信息

Clinical Laboratory, Hebei General Hospital, Shijiazhuang 050051, Hebei, China.

Hebei Clinical Research Center for Laboratory Medicine, Shijiazhuang 050051, Hebei, China.

出版信息

Aging (Albany NY). 2024 May 14;16(18):12498-12509. doi: 10.18632/aging.205799.

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.

目的

本研究探讨 SHP2 对肿瘤相关巨噬细胞（TAMs）中 STAT3/STAT6 通路的影响及其对肺腺癌增殖和转移的影响。

方法

将肺癌 A549 和 NCI-H1688 细胞系皮下注射到裸鼠体内。使用流式细胞术分离巨噬细胞，并通过 Western blot 分析 CD163、CD206 和精氨酸酶-1 水平。同样，评估了对 THP1 细胞相关蛋白的影响。通过划痕愈合、Transwell 测定和 CCK8 评估对 A549 和 NCI-H1688 细胞迁移、侵袭和增殖的影响。

结果

与对照组相比，sh-RNA SHP2 组显示肿瘤体积增大，巨噬细胞和 THP1 细胞中 CD163、CD206、精氨酸酶-1、p-STAT3、p-STAT6、IL-4、IL-10 和各种组织蛋白酶的表达水平升高。然而，p-STAT1 和 p-STAT5 水平保持不变。sh-RNA SHP2 组还显示两种细胞系的迁移、侵袭和增殖增强。