外泌体 TRIM3 是胃癌的一种新型标志物和治疗靶点。
Exosomal TRIM3 is a novel marker and therapy target for gastric cancer.
机构信息
Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China.
Center for Clinical Laboratory, the First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
出版信息
J Exp Clin Cancer Res. 2018 Jul 21;37(1):162. doi: 10.1186/s13046-018-0825-0.
BACKGROUND
Exosomes are critically involved in cancer development and progression. The exosomal contents have been suggested as ideal cancer biomarkers. In this study, we investigated the expression of exosomal proteins in the serum of gastric cancer patients and their roles in gastric cancer.
METHODS
The proteomic profile of exosomes from the serum of gastric cancer patients was detected by using LC-MS/MS. The expression of TRIM3 in exosomes from the serum of gastric cancer patients and healthy controls was assessed by ELISA and western blot. Immunohistochemistry was used to detect TRIM3 expression in gastric cancer tissues and their matching adjacent tissues. The growth and migration abilities of gastric cancer cells with TRIM3 overexpression or knockdown in vitro were evaluated by colony formation assay and transwell migration assay. The effects of TRIM3 overexpression or knockdown on gastric cancer growth and metastasis in vivo were investigated by using subcutaneous xenograft tumor and peritoneal metastasis mouse model. The effects of TRIM3-overexpressing exosomes on gastric cancer growth and metastasis in vitro and in vivo were also evaluated.
RESULTS
We found that the expression levels of TRIM3 mRNA and protein were decreased in gastric cancer tissues compared to the matched control tissues. In addition, the levels of TRIM3 protein in the serum exosomes of gastric cancer patients were lower than that in healthy controls. We demonstrated that TRIM3 overexpression reduced while TRIM3 knockdown promoted the growth and metastasis of gastric cancer in vitro and in vivo through the regulation of stem cell factors and EMT regulators. Moreover, exosomes-mediated delivery of TRIM3 protein could suppress gastric cancer growth and metastasis in vitro and in vivo.
CONCLUSIONS
Taken together, our findings suggest that exosomal TRIM3 may serve as a biomarker for gastric cancer diagnosis and the delivery of TRIM3 by exosomes may provide a new avenue for gastric cancer therapy.
背景
外泌体在癌症的发生和发展中起着至关重要的作用。外泌体的内容物被认为是理想的癌症生物标志物。在这项研究中，我们研究了胃癌患者血清中外泌体蛋白的表达及其在胃癌中的作用。
方法
采用 LC-MS/MS 检测胃癌患者血清中外泌体的蛋白质组谱。通过 ELISA 和 Western blot 评估胃癌患者和健康对照者血清中外泌体中 TRIM3 的表达。免疫组织化学检测胃癌组织及其配对的相邻组织中 TRIM3 的表达。通过集落形成实验和 Transwell 迁移实验评估体外过表达或敲低 TRIM3 对胃癌细胞生长和迁移能力的影响。通过皮下移植瘤和腹膜转移小鼠模型研究 TRIM3 过表达或敲低对体内胃癌生长和转移的影响。还评估了过表达 TRIM3 的外泌体对体外和体内胃癌生长和转移的影响。
结果
我们发现，与配对的对照组织相比，胃癌组织中 TRIM3 mRNA 和蛋白的表达水平降低。此外，胃癌患者血清外泌体中 TRIM3 蛋白水平低于健康对照组。我们证明，TRIM3 过表达减少，而 TRIM3 敲低通过调节干细胞因子和 EMT 调节剂促进胃癌在体外和体内的生长和转移。此外，外泌体介导的 TRIM3 蛋白递送可抑制胃癌在体外和体内的生长和转移。
结论
综上所述，我们的研究结果表明，外泌体 TRIM3 可作为胃癌诊断的生物标志物，外泌体递送 TRIM3 可能为胃癌治疗提供新途径。
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