Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers.
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.
Skog
Johan
J
Department of Neurology, Massachusetts General Hospital, and Neuroscience Program, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
Würdinger
Tom
T
van Rijn
Sjoerd
S
Meijer
Dimphna H
DH
Gainche
Laura
L
Sena-Esteves
Miguel
M
Curry
William T
WT
Carter
Bob S
BS
Krichevsky
Anna M
AM
Breakefield
Xandra O
XO
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D005909:Glioblastoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism; D012313:RNA / Q000378:metabolism* / Q000648:ultrastructure; D034443:RNA Transport
D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012313:RNA