FSTL1 sustains glioma stem cell stemness and promotes immunosuppressive macrophage polarization in glioblastoma

IF 9.1 1区 医学 Q1 ONCOLOGY
Fengqi Zhou , Jincheng Tao , Huiqing Gou , Shuheng Liu , Dong Yu , Junxia Zhang , Jianxiong Ji , Ning Lin , Yingyi Wang
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引用次数: 0

Abstract

Tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) play a crucial role in glioblastoma (GBM) progression by interacting with glioma stem cells (GSCs). These interactions lead to the polarization of TAMs toward an M2 phenotype, which, in turn, enhances the stem-like traits and malignant progression of GSCs. Our study shows that FSTL1, a protein released by GSCs, is significantly elevated in gliomas and linked to the progression of the disease. By suppressing FSTL1 in a mouse model, we observed reduced tumor growth and a decrease in M2 macrophages. In vitro studies show that FSTL1 from GSCs promotes M2 polarization and infiltration. Importantly, GSCs utilize autocrine FSTL1 to interact with TLR2, which inhibits the endocytosis-lysosomal degradation pathway mediated by EGFR, resulting in the activation of the PI3K-AKT signaling pathway that is critical for maintaining their self-renewal. These findings underscore the importance of FSTL1 in GSC maintenance and M2 macrophage polarization, suggesting that interventions targeting the FSTL1/TLR2 pathway could provide a novel therapeutic approach for GBM patients.
FSTL1在胶质母细胞瘤中维持胶质瘤干细胞的干性并促进免疫抑制性巨噬细胞极化。
肿瘤微环境(TME)中的肿瘤相关巨噬细胞(tam)通过与胶质瘤干细胞(GSCs)相互作用,在胶质母细胞瘤(GBM)的进展中起着至关重要的作用。这些相互作用导致tam向M2表型极化,这反过来又增强了GSCs的茎样性状和恶性进展。我们的研究表明,FSTL1,一种由GSCs释放的蛋白质,在胶质瘤中显著升高,并与疾病的进展有关。通过在小鼠模型中抑制FSTL1,我们观察到肿瘤生长减少,M2巨噬细胞减少。体外研究表明,来自GSCs的FSTL1促进M2极化和浸润。重要的是,GSCs利用自分泌FSTL1与TLR2相互作用,从而抑制EGFR介导的内吞-溶酶体降解途径,从而激活PI3K-AKT信号通路,这对维持其自我更新至关重要。这些发现强调了FSTL1在GSC维持和M2巨噬细胞极化中的重要性,表明针对FSTL1/TLR2通路的干预可能为GBM患者提供一种新的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer letters
Cancer letters 医学-肿瘤学
CiteScore
17.70
自引率
2.10%
发文量
427
审稿时长
15 days
期刊介绍: Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.
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