Skog Johan, Würdinger Tom, van Rijn Sjoerd, Meijer Dimphna H, Gainche Laura, Sena-Esteves Miguel, Curry William T, Carter Bob S, Krichevsky Anna M, Breakefield Xandra O
Department of Neurology, Massachusetts General Hospital, and Neuroscience Program, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
Nat Cell Biol. 2008 Dec;10(12):1470-6. doi: 10.1038/ncb1800. Epub 2008 Nov 16.
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.
胶质母细胞瘤肿瘤细胞释放包含mRNA、miRNA和血管生成蛋白的微泡（外泌体）。这些微泡被正常宿主细胞摄取，如脑微血管内皮细胞。通过将一种报告蛋白的mRNA整合到这些微泡中，我们证明微泡传递的信息可被受体细胞翻译。这些微泡还富含血管生成蛋白，并刺激内皮细胞形成小管。因此，肿瘤衍生的微泡可作为在肿瘤环境中将遗传信息和蛋白质传递给受体细胞的一种方式。胶质母细胞瘤微泡还刺激了人胶质瘤细胞系的增殖，表明其具有自我促进的特性。在胶质母细胞瘤患者的血清微泡中可检测到胶质瘤特有的信使RNA突变体/变体和miRNA。在25例胶质母细胞瘤患者中的7例血清微泡中检测到肿瘤特异性表皮生长因子受体变体III（EGFRvIII）。因此，肿瘤衍生的微泡可能通过血液检测为癌症患者提供诊断信息并辅助治疗决策。
