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

被引:3897
作者
Skog, Johan [1 ,2 ,3 ]
Wuerdinger, Tom [1 ,2 ,3 ,4 ]
van Rijn, Sjoerd [1 ,2 ,3 ]
Meijer, Dimphna H. [1 ,2 ,3 ]
Gainche, Laura [1 ,2 ,3 ]
Sena-Esteves, Miguel [1 ,2 ,3 ]
Curry, William T., Jr. [5 ]
Carter, Bob S. [5 ]
Krichevsky, Anna M. [6 ]
Breakefield, Xandra O. [1 ,2 ,3 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA
[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA
[3] Harvard Univ, Sch Med, Neurosci Program, Charlestown, MA 02129 USA
[4] VU Med Ctr, Dept Neurosurg, Neurooncol Res Grp, Canc Ctr Amsterdam, NL-1007 MB Amsterdam, Netherlands
[5] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA
[6] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA
关键词
D O I
10.1038/ncb1800
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1470 / U209
页数:12
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