胃癌来源exosomes诱导间充质干细胞促进裸鼠皮下移植瘤生长

摘要

Objective:To investigate whether cancer cell-derived exosomes induced mesenchymal stem cells (MSCs) could high express EMT associate gene and promote tumor incidence.Methods:SGC7901 derived exosomes were isolated and purified by a modification of the differential centrifugation and purification on sucrose cushion procedure.The expression of EMT maker in hucMSCs was detection by Western blot.Xenograft experiments observe the incidence of xenografts in nude mice.Results:We first showed that gastric cancer cell-derived exosomes induced the expression of EMT markers in hucMSCs.And our results also showed that SGC7901 derived exosomes promoted tumor incidence in vivo.Conclusion:hucMSCs was high expressed EMT associated genes after treated with gastric cancer cells exosomes and promote the incidence of tumor xenografts in nude mice.%目的:探讨胃癌细胞(SGC7901细胞)来源exosomes作用于人脐带来源间充质干细胞(human umbilical cord mesenchymal stem cells,hucMSCs)其EMT(epithelial-mesenchymal transition)相关分子表达以及对SGC7901细胞裸鼠皮下移植瘤的影响.方法:采用离心超滤和蔗糖密度梯度超速离心方法从胃癌细胞株SGC7901细胞的培养上清液中分离出胃癌细胞exosomes,透射电子显微镜观察其大小和形态,Western blot检测其标志性蛋白CD9和CD81的表达.Western blot分析SGC7901细胞分泌exosomes作用于hucMSCs后其EMT相关分子TGF-β、IL-6和N-cadherin的表达水平;裸鼠皮下移植瘤实验观察裸鼠移植瘤的生长情况.结果:透射电子显微镜下观察SG7901-exosomes具有椭圆或碟状的囊泡结构;直径在30 ～ 100 nm之间,表达CD9和CD81蛋白;SGC7901-exosomes作用于hucMSCs后其EMT相关分子TGF-β、IL-6和N-cadherin的表达水平升高;且SGC7901-exosomes诱导过的hucMSCs能促进裸鼠皮下肿瘤的发生和发展.结论:SGC7901分泌的exosomes能促进hucMSCs高表达TGF-β、IL-6和N-cadherin;能促进SGC7901细胞裸鼠皮下移植瘤的发生和生长.