M2型巨噬细胞分泌SIGLEC11增强食管鳞癌细胞干性促进转移OA

Objective This study investigates the expression profile of sialic acid-binding immuno-globulin-like lectin 11(SIGLEC11)in esophageal squamous cell carcinoma(ESCC)and elucidates its role in maintaining tumor stemness and promoting invasion and metastasis.We further evaluated whether SIGLEC11 acts as a key pro-tumorigenic molecule mediated by M2 macrophages,thereby providing theo-retical support for understanding the regulatory mechanisms of the ESCC immune microenvironment and identifying potential therapeutic targets.Methods Proteomic analysis was performed to compare the sec-retome profiles of M0,M1,and M2 macrophages differentiated from THP-1 monocytes.The expression levels of SIGLEC11 in different macrophage subtypes were validated using qPCR,western blotting,and multiplex immunofluorescence,and its association with immune-cell infiltration was assessed via the TIMER2 database.Sphere formation assays and Transwell migration/invasion assays were conducted to evaluate the effects of exogenous recombinant SIGLEC11 protein on the stemness maintenance and motil-ity of ESCC cell lines KYSE30,KYSE180,and KYSE510.Kaplan-Meier survival analysis and clinico-pathological correlation analyses were performed based on publicly available datasets to determine the association between SIGLEC11 expression and patient prognosis.Results Proteomic screening and sub-sequent validation at both the protein and transcript levels demonstrated that SIGLEC11 was specifically and highly expressed in M2 macrophages and could be released via a secretory pathway.TIMER2 analy-sis indicated a positive correlation between SIGLEC11 expression and macrophage infiltration.Functional in vitro assays showed that exogenous SIGLEC11 significantly enhanced the self-renewal,migration,and invasion capacities of ESCC cells,suggesting its promotive effect on tumor stemness.Analysis of the TCGA database demonstrated that SIGLEC11 expression was closely associated with tumor aggressive-ness,and survival analysis further indicated that high SIGLEC11 expression correlated with poor patient prognosis.Conclusion SIGLEC11 is specifically upregulated in M2-polarized macrophages,where it functions to enhance tumor stemness and to promote the migration and invasion of ESCC cells.Its expres-sion is closely associated with tumor malignancy and with unfavorable clinical outcomes.These findings suggest that SIGLEC11 serves as a pivotal molecular hub linking the tumor immune microenvironment to the malignant phenotype of ESCC,highlighting its potential as a novel therapeutic target for diagnosis,prognostic assessment,and immunotherapy in ESCC.