|Table of Contents|

Molecular mechanism of hepatocellular carcinoma cell exosome-induced STAT3 phosphorylation promoting macrophage polarization

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2025 06
Page:
918-923
Research Field:
Publishing date:

Info

Title:
Molecular mechanism of hepatocellular carcinoma cell exosome-induced STAT3 phosphorylation promoting macrophage polarization
Author(s):
YAN Jianzhou; YANG Yafei; ZHANG Wenquan
Department of Hepatobiliary and Pancreatic Surgery,The NO.2 People's Hospital of Lanzhou,Gansu Lanzhou 730046,China.
Keywords:
liver cancer; exosome; STAT3; phosphorylation; macrophage; polarization; FGD5-AS1
PACS:
R735.7
DOI:
10.3969/j.issn.1672-4992.2025.06.005
Abstract:
Objective:To investigate the molecular mechanism of hepatocellular carcinoma cell exosome-induced STAT3 phosphorylation promoting macrophage M2 polarization.Methods:The M2 polarization level of macrophages was quantitatively detected by flow cytometry and real-time fluorescence.The cell surface markers CD206 of M2 macrophages were detected by flow cytometry,and the expression levels of IL-12A,TNF and NOS2 of M2 macrophages markers IL-10,ARG1,TGFB1 and M1 macrophages were detected by real-time quantitative PCR.Under the following conditions:Macrophages were co-cultured with normal hepatocytes or hepatocellular carcinoma cells.Macrophages were treated by exosomes of normal hepatocytes or hepatocellular carcinoma cells.After overexpression or knockdown of FGD5-AS1.STAT3 phosphorylation inhibitor SC144 or FLLL32 treatment.Results:Compared with normal hepatocytes,co-culture with hepatocellular carcinoma cells could induce macrophages to express macrophage markers CD206,IL-10,ARG1 and TGFB1 of M2 type(P＜0.05),while the expression levels of IL-12A,TNF and NOS2 of M1 type macrophage markers were decreased(P＜0.05).Compared with normal hepatocytes,exosomes of hepatocellular carcinoma cells can promote the expression of CD206,IL-10,ARG1 and TGFB1 in macrophages(P＜0.05),and inhibit the expression levels of IL-12A,TNF and NOS2(P＜0.05).After FGD5-AS1 was knocked down in macrophages,the expressions of CD206,IL-10,ARG1 and TGFB1 were inhibited(P＜0.05),and the expressions of IL-12A,TNF and NOS2 were promoted(P＜0.05).After overexpression of FGD5-AS1 in macrophages,the expressions of CD206,IL-10,ARG1 and TGFB1 in macrophages were promoted(P＜0.05),and the expressions of IL-12A,TNF and NOS2 were inhibited(P＜0.05).After exosome treatment of normal hepatocytes overexpressing FGD5-AS1,the expressions of CD206,IL-10,ARG1 and TGFB1 in macrophages were promoted(P＜0.05),and the expressions of IL-12A,TNF and NOS2 were inhibited(P＜0.05).The expression of CD206,IL-10,ARG1 and TGFB1 in macrophages was inhibited(P＜0.05),and the expression of IL-12A,TNF and NOS2 was promoted(P＜0.05) after exosome treatment of liver cancer cells with FGD5-AS1 knocked down(P＜0.05).After knocking down FGD5-AS1 in macrophages,the phosphorylation level of STAT3 in macrophages decreased.After overexpression of FGD5-AS1 in macrophages,the phosphorylation level of STAT3 in macrophages increased.The expression levels of M2-type macrophage markers CD206,IL-10,ARG1,TGFB1 and M1-type macrophage markers IL-12A,TNF and NOS2 in macrophages were not significantly changed after treatment with STAT3 phosphorylation inhibitor SC144 or FLLL32 and exosomes of hepatoma cells.Conclusion:Exosomes containing FGD5-AS1 secreted by hepatocellular carcinoma cells can induce the phosphorylation of STAT3 in macrophages,and subsequently promote the M2-type polarization of macrophages.

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