Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers

胶质母细胞瘤微泡运输促进肿瘤生长并提供诊断生物标志物的 RNA 和蛋白质

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作者:Johan Skog, Tom Würdinger, Sjoerd van Rijn, Dimphna H Meijer, Laura Gainche, Miguel Sena-Esteves, William T Curry Jr, Bob S Carter, Anna M Krichevsky, Xandra O Breakefield

Abstract

Glioblastoma tumour cells release microvesicles (exosomes) containing mRNA, miRNA and angiogenic proteins. These microvesicles are taken up by normal host cells, such as brain microvascular endothelial cells. By incorporating an mRNA for a reporter protein into these microvesicles, we demonstrate that messages delivered by microvesicles are translated by recipient cells. These microvesicles are also enriched in angiogenic proteins and stimulate tubule formation by endothelial cells. Tumour-derived microvesicles therefore serve as a means of delivering genetic information and proteins to recipient cells in the tumour environment. Glioblastoma microvesicles also stimulated proliferation of a human glioma cell line, indicating a self-promoting aspect. Messenger RNA mutant/variants and miRNAs characteristic of gliomas could be detected in serum microvesicles of glioblastoma patients. The tumour-specific EGFRvIII was detected in serum microvesicles from 7 out of 25 glioblastoma patients. Thus, tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test.

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