Nature子刊:中科院廣州生物院陳小平研究組揭示瘧原蟲感染小鼠血漿外泌體抑制腫瘤血管生成的分子機(jī)制

 2017年6月26日，國際學(xué)術(shù)權(quán)威刊物自然出版集團(tuán)旗下子刊《Oncogenesis》雜志上在線發(fā)表了中國科學(xué)院廣州生物醫(yī)藥與健康研究院陳小平課題組的新研究成果“Exosomes from Plasmodium-infected hosts inhibit tumor angiogenesis in a murine Lewis lung cancer model”。研究發(fā)現(xiàn)瘧原蟲感染小鼠血漿外泌體(exosomes)能夠抑制腫瘤血管生成，并初步闡明其分子機(jī)制。研究加深了對(duì)瘧原蟲感染宿主所分泌的外泌體與腫瘤血管生成之間的相互作用的認(rèn)識(shí)，為開發(fā)瘧原蟲感染來源的外泌體作為一種新型抗腫瘤制劑奠定了基礎(chǔ)。博士研究生楊一峻為論文作者，陳小平博士為論文通訊作者。
外泌體是細(xì)胞外膜泡，在細(xì)胞與細(xì)胞間通訊中起作用。在病原體感染宿主時(shí)，外泌體也發(fā)揮重要作用。但是，在上述論文發(fā)表之前，科學(xué)家們并不清楚瘧原蟲感染宿主所產(chǎn)生的外泌體是否能夠抑制腫瘤血管生成，更不知道其中的分子機(jī)制。
研究人員選用肺癌小鼠模型作為研究對(duì)象，從感染瘧原蟲的小鼠血漿中獲得外泌體，并將這些外泌體注射到小鼠的腫瘤內(nèi)部，并與沒有瘧原蟲感染的小鼠血漿外泌體進(jìn)行對(duì)照。研究發(fā)現(xiàn)，瘧原蟲感染小鼠的血漿外泌體顯著抑制腫瘤血管的生成。進(jìn)一步的研究發(fā)現(xiàn)，瘧原蟲感染的小鼠血漿外泌體通過至少四種特殊的微小RNA(miR16-5p/17-5p/322-5p/497-5p)抑制血管內(nèi)皮細(xì)胞 VEGF受體(VEGFR2)的 表達(dá)從而阻斷血管生成的信號(hào)通路。這些發(fā)現(xiàn)加深了人們對(duì)瘧原蟲抗癌機(jī)理的理解，并為瘧原蟲療法治療癌癥的臨床研究提供進(jìn)一步的理論依據(jù)。

瘧原蟲感染小鼠血漿外泌體抑制腫瘤血管生成的分子機(jī)制

原文鏈接：
Exosomes from Plasmodium-infected hosts inhibit tumor angiogenesis in a murine Lewis lung cancer model

原文摘要：
Previous research to investigate the interaction between malaria infection and tumor progression has revealed that malaria infection can potentiate host immune response against tumor in tumor-bearing mice. Exosomes may play key roles in disseminating pathogenic host-derived molecules during infection because several studies have shown the involvement and roles of extracellular vesicles in cell–cell communication. However, the role of exosomes generated during Plasmodium infection in tumor growth, progression and angiogenesis has not been studied either in animals or in the clinics. To test this hypothesis, we designed an animal model to generate and isolate exosomes from mice which were subsequently used to treat the tumor. Intra-tumor injection of exosomes derived from the plasma of Plasmodium-infected mice provided significantly reduced Lewis lung cancer growth in mice. We further co-cultured the isolated exosomes with endothelial cells and observed significantly reduced ex[x]pression of VEGFR2 and migration in the endothelial cells. Interestingly, high level of micro-RNA (miRNA) 16/322/497/17 was detected in the exosomes derived from the plasma of mice infected with Plasmodium compared with those from control mice. We observed that overex[x]pression of the miRNA 16/322/497/17 in endothelial cell corresponded with decreased ex[x]pression of VEGFR2, inhibition of angiogenesis and inhibition of the miRNA 16/322/497/17 significantly alleviated these effects. These data provide novel scientific evidence of the interaction between Plasmodium infection and lung cancer growth and angiogenesis.