Yuechao Yang , Huanhuan Cui , Deheng Li , Lei Chen , Yi Liu , Changshuai Zhou , Liangdong Li , Mingtao Feng , Xin Chen , Yiqun Cao , Yang Gao
{"title":"S100A8 在胶质瘤中通过 TLR4/IL-10 信号通路诱导小胶质细胞表型极化，从而促进肿瘤进展","authors":"Yuechao Yang , Huanhuan Cui , Deheng Li , Lei Chen , Yi Liu , Changshuai Zhou , Liangdong Li , Mingtao Feng , Xin Chen , Yiqun Cao , Yang Gao","doi":"10.1016/j.jncc.2024.07.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <em>in vivo</em> and <em>in vitro</em> 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.</div></div><div><h3>Results</h3><div>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. <em>In vivo</em> 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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 4","pages":"Pages 369-381"},"PeriodicalIF":7.6000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma\",\"authors\":\"Yuechao Yang , Huanhuan Cui , Deheng Li , Lei Chen , Yi Liu , Changshuai Zhou , Liangdong Li , Mingtao Feng , Xin Chen , Yiqun Cao , Yang Gao\",\"doi\":\"10.1016/j.jncc.2024.07.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <em>in vivo</em> and <em>in vitro</em> 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.</div></div><div><h3>Results</h3><div>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. <em>In vivo</em> 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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>\",\"PeriodicalId\":73987,\"journal\":{\"name\":\"Journal of the National Cancer Center\",\"volume\":\"4 4\",\"pages\":\"Pages 369-381\"},\"PeriodicalIF\":7.6000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the National Cancer Center\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2667005424000784\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the National Cancer Center","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2667005424000784","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma
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.
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