美國(guó)科學(xué)家近日通過研究,,從膠質(zhì)母細(xì)胞瘤(glioblastoma,腦瘤的一種)患者血液中名為外來體(exosome)的微泡中發(fā)現(xiàn)了腫瘤相關(guān)的RNA和蛋白,,它們能通過特殊的方式促進(jìn)腫瘤生長(zhǎng),。這是首次對(duì)來自膠質(zhì)母細(xì)胞瘤細(xì)胞的外來體內(nèi)容物的詳細(xì)分析,可能有助指導(dǎo)致命腦瘤的治療,。相關(guān)論文11月16日在線發(fā)表于《自然—細(xì)胞生物學(xué)》(Nature Cell Biology),。
許多種類的細(xì)胞均會(huì)分泌外來體,作為正常細(xì)胞通訊的一部分,。此前,,科學(xué)家已知數(shù)類腫瘤分泌包含特殊蛋白的外來體,它們能改變細(xì)胞環(huán)境從而促進(jìn)腫瘤生長(zhǎng),。美國(guó)麻省綜合醫(yī)院的Xandra Breakefield和同事首先分析了三個(gè)膠質(zhì)母細(xì)胞瘤患者的腫瘤細(xì)胞,,證實(shí)這些細(xì)胞分泌了包含RNA和蛋白分子的外來體。將膠質(zhì)母細(xì)胞瘤外來體與正常細(xì)胞混合培養(yǎng),,腫瘤RNA會(huì)被遞送到正常細(xì)胞內(nèi),,并產(chǎn)生它的編碼蛋白。
隨后,,研究人員分析了25名患者的腫瘤組織和血清,,結(jié)果發(fā)現(xiàn),在某些組織樣本中,,表皮生長(zhǎng)因子受體(EGFR)中的某個(gè)突變會(huì)表現(xiàn)為腫瘤亞型,。在2個(gè)患者中,研究人員通過外來體分析確定了某個(gè)并未出現(xiàn)在腫瘤組織樣本中的EGFR突變,。這表明,,因?yàn)槟[瘤細(xì)胞經(jīng)常無序的多樣性,外科活組織檢查很可能錯(cuò)過包含關(guān)鍵信息的組織,。
論文第一作者Johan Skog說:“膠質(zhì)母細(xì)胞瘤分泌足夠的外來體以穿越血-腦屏障,。我們能夠分離它們,,分析RNA轉(zhuǎn)錄,并顯示如何利用它們作為生物標(biāo)記來指導(dǎo)標(biāo)靶治療和監(jiān)控治療反應(yīng),。將來,,外來體也有可能被用于向腫瘤位點(diǎn)遞送治療分子。”(生物谷Bioon.com)
生物谷推薦原始出處:
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.