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细胞外囊泡介导的脑胶质母细胞瘤血管病变。

Extracellular Vesicle Mediated Vascular Pathology in Glioblastoma.

机构信息

McGill University and the Research Institute of the McGill University Health Centre, QC, Canada.

出版信息

Subcell Biochem. 2021;97:247-273. doi: 10.1007/978-3-030-67171-6_10.

Abstract

Glioblastoma (GBM) is an incurable, infiltrative high-grade brain tumour associated with dramatic vascular responses observed both locally (angiogenesis, vascular cooption, angiocrine effects, microthrombosis) and systemically (venous thromboembolism). GBM-associated vascular pathology is diagnostically relevant and constitutes a source of morbidity, mortality and progressive changes in tumour biology. Extracellular vesicles (EVs) have emerged as unique mediators of vascular effects in brain tumours acting as vehicles for intercellular transfer of oncoproteins (e.g. EGFRvIII), RNA, DNA and molecular effectors of angiogenesis and thrombosis. Vascular effects of GBM EVs are regulated by cancer cell genome, epigenome and microenvironment and differ between subtypes of cancer cells and stem cells. Understanding and targeting EV-driven vascular processes in GBM may offer new approaches to diagnose and treat these intractable tumours.

摘要

胶质母细胞瘤(GBM)是一种无法治愈的浸润性高级别脑肿瘤,伴有局部(血管生成、血管选择、血管内分泌作用、微血管血栓形成)和全身(静脉血栓栓塞)的剧烈血管反应。与 GBM 相关的血管病变具有诊断意义,是发病率、死亡率和肿瘤生物学进行性变化的一个来源。细胞外囊泡(EVs)已成为脑肿瘤中血管作用的独特介质,作为致癌蛋白(如 EGFRvIII)、RNA、DNA 和血管生成和血栓形成的分子效应物在细胞间转移的载体。GBM EVs 的血管作用受癌细胞基因组、表观基因组和微环境调节,并且在癌细胞和干细胞的亚类之间存在差异。了解和靶向 GBM 中 EV 驱动的血管过程可能为诊断和治疗这些难治性肿瘤提供新方法。

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