S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma

Abstract

Background

S100A8 is a member of the S100 protein family and plays a pivotal role in regulating inflammation and tumor progression. This study aimed to comprehensively assess the expression patterns and functional roles of S100A8 in glioma progression.

Methods

Glioma tissues were collected from 98 patients who underwent surgical treatment at Fudan University Shanghai Cancer Center. S100A8 expression in glioma tissues was analyzed using immunohistochemistry (IHC) to establish its correlation with clinicopathological features in patients. The expression and prognostic effect of S100A8 in glioma were analyzed using TCGA and CGGA public databases. Then, we investigated the role of S100A8 in glioma through a series of in vivo and in vitro experiments including Transwell, wound healing, CCK8, and intracranial tumor models. Subsequently, bioinformatics analysis, single-cell sequencing and coimmunoprecipitation (Co-IP) were used to explore the underlying mechanism.

Results

S100A8 was upregulated in gliomas compared to paracancerous tissues, and this phenotype was significantly correlated with poor prognosis. Subgroup analysis showed that S100A8 expression was higher in the high-grade glioma (HGG) group than that in the low-grade glioma (LGG) group. S100A8 overexpression in glioma cell lines promoted cell proliferation, migration and invasion, while silencing S100A8 reversed these effects. In vivo experiments showed that S100A8 knockdown can significantly reduce the tumor burden of glioma cells. Notably, S100A8 was observed to stimulate microglial M2 polarization by interacting with TLR4, which subsequently induced NF-κB signaling and IL-10 secretion within the tumor microenvironment.

Conclusions

S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma. It might represent a therapeutic target for further basic research or clinical management of glioma.