美国科学家近日通过研究,从胶质母细胞瘤(glioblastoma,脑瘤的一种)患者血液中名为外来体(exosome)的微泡中发现了肿瘤相关的RNA和蛋白,它们能通过特殊的方式促进肿瘤生长。这是首次对来自胶质母细胞瘤细胞的外来体内容物的详细分析,可能有助指导致命脑瘤的治疗。相关论文11月16日在线发表于《自然—细胞生物学》(Nature Cell Biology)。
许多种类的细胞均会分泌外来体,作为正常细胞通讯的一部分。此前,科学家已知数类肿瘤分泌包含特殊蛋白的外来体,它们能改变细胞环境从而促进肿瘤生长。美国麻省综合医院的Xandra Breakefield和同事首先分析了三个胶质母细胞瘤患者的肿瘤细胞,证实这些细胞分泌了包含RNA和蛋白分子的外来体。将胶质母细胞瘤外来体与正常细胞混合培养,肿瘤RNA会被递送到正常细胞内,并产生它的编码蛋白。
随后,研究人员分析了25名患者的肿瘤组织和血清,结果发现,在某些组织样本中,表皮生长因子受体(EGFR)中的某个突变会表现为肿瘤亚型。在2个患者中,研究人员通过外来体分析确定了某个并未出现在肿瘤组织样本中的EGFR突变。这表明,因为肿瘤细胞经常无序的多样性,外科活组织检查很可能错过包含关键信息的组织。
论文第一作者Johan Skog说:“胶质母细胞瘤分泌足够的外来体以穿越血-脑屏障。我们能够分离它们,分析RNA转录,并显示如何利用它们作为生物标记来指导标靶治疗和监控治疗反应。将来,外来体也有可能被用于向肿瘤位点递送治疗分子。”(生物谷Bioon.com)
生物谷推荐原始出处:
Nature Cell Biology,doi:10.1038/ncb1800,Johan Skog,Xandra O. Breakefield
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.