Letter abstract
Nature Cell Biology 10, 1470 - 1476 (2008)
Published online: 16 November 2008 | doi:10.1038/ncb1800
Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers
Johan Skog1, Tom Würdinger1,2, Sjoerd van Rijn1, Dimphna H. Meijer1, Laura Gainche1, William T. Curry, Jr.3, Bob S. Carter3, Anna M. Krichevsky4 & Xandra O. Breakefield1
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.
- Departments of Neurology and Radiology, Massachusetts General Hospital, and Neuroscience Program, Harvard Medical School, 149 13th Street, Charlestown, MA02129, USA.
- Neuro-oncology Research Group, Department of Neurosurgery, Cancer Center Amsterdam, VU Medical Center, Amsterdam 1007 MB, The Netherlands.
- Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Yawkey 9 Fruit Street, Boston, MA02114, USA.
- Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, 4 Blackfan Circle, Boston MA02115, USA.
Correspondence to: Xandra O. Breakefield1 e-mail: breakefield@hms.harvard.edu
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