Microvascular proliferation is a key feature of glioblastoma and neovascularization has been implicated in tumor progression. Glioblastomas use pro-angiogenic factors such as vascular endothelial growth factor (VEGF) for new blood vessel formation. Yet, anti-VEGF therapy does not prolong overall survival so that alternative angiogenic pathways may need to be explored as drug targets. Both glioma cells and glioma-associated endothelial cells produce TGF-β superfamily ligands which bind TGF-β receptors (TGF-βR). The TGF-βR type III endoglin (CD105), is a marker of proliferating endothelium that has already been studied as a potential therapeutic target. We studied endoglin expression in glioblastoma tissue and in glioma-associated endothelial cells in a cohort of 52 newly diagnosed and 10 recurrent glioblastoma patients by immunohistochemistry and by ex vivo single-cell gene expression profiling of 6 tumors. Endoglin protein levels were similar in tumor stroma and endothelium and correlated within tumors. Similarly, endoglin mRNA determined by ex vivo single-cell gene expression profiling was expressed in both compartments. There was positive correlation between endoglin and proteins of TGF-β superfamily signaling. No prognostic role of endoglin expression in either compartment was identified. Endoglin gene silencing in T98G glioma cells and in human cerebral microvascular endothelial cells (hCMEC) did not affect constitutive or exogenous TGF-β superfamily ligand-dependent signaling, except for a minor facilitation of pSmad1/5 signaling in hCMEC. These observations challenge the notion that endoglin might become a promising therapeutic target in glioblastoma.

中文翻译：

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胶质母细胞瘤中的内皮糖蛋白和 TGF-β 信号转导

微血管增殖是胶质母细胞瘤的一个关键特征，新血管形成与肿瘤进展有关。胶质母细胞瘤使用促血管生成因子，例如血管内皮生长因子 (VEGF) 来形成新血管。然而，抗 VEGF 治疗不会延长总生存期，因此可能需要探索替代的血管生成途径作为药物靶点。神经胶质瘤细胞和神经胶质瘤相关的内皮细胞都会产生结合 TGF-β 受体 (TGF-βR) 的 TGF-β 超家族配体。TGF-βR III 型内皮糖蛋白 (CD105) 是增殖内皮的标志物，已被研究为潜在的治疗靶点。我们通过免疫组织化学和 6 种肿瘤的离体单细胞基因表达谱研究了 52 名新诊断和 10 名复发性胶质母细胞瘤患者队列中胶质母细胞瘤组织和胶质瘤相关内皮细胞中的内皮糖蛋白表达。内皮糖蛋白水平在肿瘤基质和内皮中相似，并且在肿瘤内相关。同样，通过离体单细胞基因表达谱确定的内皮糖蛋白 mRNA 在两个隔室中都有表达。内皮糖蛋白与 TGF-β 超家族信号蛋白之间存在正相关关系。未鉴定出任一隔室中内皮糖蛋白表达的预后作用。T98G 神经胶质瘤细胞和人脑微血管内皮细胞 (hCMEC) 中的内皮糖蛋白基因沉默不影响组成型或外源性 TGF-β 超家族配体依赖性信号传导，除了 hCMEC 中 pSmad1/5 信号的轻微促进。这些观察结果对内皮糖蛋白可能成为胶质母细胞瘤有希望的治疗靶点的观点提出了挑战。