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文章:

髓母细胞瘤微环境中NRP1与GFAP的表达:对血管生成及肿瘤进展的影响

NRP1 and GFAP Expression in the Medulloblastoma Microenvironment: Implications for Angiogenesis and Tumor Progression

原文发布日期:22 July 2025

DOI: 10.3390/cancers17152417

类型: Article

开放获取: 是

 

英文摘要:

Background/Objectives: Medulloblastoma (MB) is the second leading cause of cancer-related death in children. Its tumor microenvironment (TME) includes endothelial, glial, and immune cells that influence tumor architecture and progression. Neuropilin-1 (NRP1), a co-receptor for semaphorins and vascular endothelial growth factor (VEGF), is expressed in various cell types during oncogenesis, yet its role in MB progression remains unclear. This study aimed to evaluate the expression and localization of NRP1 and glial fibrillary acidic protein (GFAP) in MB tissue.Methods: We analyzed MB tissue samples using immunohistochemistry, immunofluorescence, and quantitative PCR. Samples were stratified by molecular subgroup (WNT, SHH, non-WNT/non-SHH). We assessed NRP1 expression in tumor-associated microglia/macrophages (TAMs) and endothelial cells, as well as GFAP expression in astrocytes and tumor cells. Histopathological correlations and survival analyses were also conducted.Results: NRP1 was consistently expressed by TAMs across all MB molecular subgroups. Tumor vasculature showed strong endothelial NRP1 expression, while perivascular astrocytic coverage was frequently absent. Astrocytic processes exhibited spatial differences according to tumor histology. In SHH-MBs, a subset of tumor cells showed aberrant GFAP expression, which correlated with tumor recurrence or progression.Conclusions: NRP1 and GFAP display distinct expression patterns within the MB microenvironment, reflecting subgroup-specific biological behavior. Endothelial NRP1 positivity combined with limited vascular-astrocytic interaction and aberrant GFAP expression in SHH-MB may contribute to dysregulated angiogenesis and tumor progression. These findings warrant further investigation to explore their prognostic and therapeutic implications.

 

摘要翻译: 

**背景/目的:** 髓母细胞瘤是儿童癌症相关死亡的第二大原因。其肿瘤微环境包含内皮细胞、胶质细胞和免疫细胞,这些细胞影响着肿瘤的结构和进展。神经纤毛蛋白-1是信号素和血管内皮生长因子的共受体,在肿瘤发生过程中于多种细胞类型中表达,但其在髓母细胞瘤进展中的作用尚不清楚。本研究旨在评估NRP1和胶质纤维酸性蛋白在髓母细胞瘤组织中的表达和定位。 **方法:** 我们采用免疫组织化学、免疫荧光和定量PCR技术分析了髓母细胞瘤组织样本。样本按分子亚组(WNT、SHH、非WNT/非SHH)进行分层。我们评估了NRP1在肿瘤相关小胶质细胞/巨噬细胞和内皮细胞中的表达,以及GFAP在星形胶质细胞和肿瘤细胞中的表达。同时进行了组织病理学相关性分析和生存分析。 **结果:** NRP1在所有髓母细胞瘤分子亚组的肿瘤相关小胶质细胞/巨噬细胞中均有持续表达。肿瘤脉管系统显示内皮细胞NRP1强表达,而血管周围星形胶质细胞覆盖常缺失。星形胶质细胞突起的空间分布因肿瘤组织学类型而异。在SHH亚型髓母细胞瘤中,一部分肿瘤细胞表现出异常的GFAP表达,这与肿瘤复发或进展相关。 **结论:** NRP1和GFAP在髓母细胞瘤微环境中表现出不同的表达模式,反映了亚组特异性的生物学行为。内皮细胞NRP1阳性表达,结合有限的血管-星形胶质细胞相互作用以及SHH亚型髓母细胞瘤中异常的GFAP表达,可能共同导致了血管生成失调和肿瘤进展。这些发现值得进一步研究,以探讨其预后和治疗意义。

 

 

原文链接:

NRP1 and GFAP Expression in the Medulloblastoma Microenvironment: Implications for Angiogenesis and Tumor Progression

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