Exosomal TRIM3 is a novel marker and therapy target for gastric cancer.
Exosomal TRIM3 is a novel marker and therapy target for gastric cancer.
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外泌体 TRIM3 是胃癌的新标志物和治疗靶点
DOI：
10.1186/s13046-018-0825-0
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发表时间：
2018-07-21
期刊：
影响因子：
--
通讯作者：
Xu W
中科院分区：
文献类型：
--
作者：
Fu H;Yang H;Zhang X;Wang B;Mao J;Li X;Wang M;Zhang B;Sun Z;Qian H;Xu W
背景外泌体在癌症的发生和发展中起着重要作用。外泌体内容物已被认为是理想的肿瘤生物标志物。方法采用LC-MS/MS技术检测胃癌患者血清中exosomes蛋白质组学特征，采用ELISA和western blot技术检测胃癌患者和健康对照血清中exosomes中TRIM 3蛋白的表达。采用免疫组化法检测胃癌组织及其癌旁组织中TRIM 3的表达。采用集落形成实验和transwell迁移实验检测TRIM 3过表达或敲低的胃癌细胞体外生长和迁移能力。采用小鼠皮下移植瘤和腹腔转移模型，研究TRIM 3过表达或敲低对胃癌生长和转移的影响。TRIM 3过表达的exosomes对胃癌的生长和转移的影响在体外和体内也evaluated.ResultsWe发现，TRIM 3的mRNA和蛋白的表达水平在胃癌组织中相比，匹配的对照组织降低。此外，胃癌患者血清外泌体中TRIM 3蛋白水平低于健康对照。我们证明TRIM 3过表达减少，而TRIM 3敲低通过干细胞因子和EMT调节因子的调节促进体外和体内胃癌的生长和转移。此外，外泌体介导的TRIM 3蛋白在体内外均能抑制胃癌的生长和转移。ConclusionsTwo-way，我们的研究结果表明，外泌体TRIM 3可能作为胃癌诊断的生物标志物，外泌体介导的TRIM 3蛋白的表达可能为胃癌的治疗提供新的途径。
BackgroundExosomes 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.MethodsThe 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.ResultsWe 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.ConclusionsTaken 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.
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影响因子：
8
作者：
通讯作者：
--
影响因子：
21.3
作者：
Costa-Silva B;Aiello NM;Ocean AJ;Singh S;Zhang H;Thakur BK;Becker A;Hoshino A;Mark MT;Molina H;Xiang J;Zhang T;Theilen TM;García-Santos G;Williams C;Ararso Y;Huang Y;Rodrigues G;Shen TL;Labori KJ;Lothe IM;Kure EH;Hernandez J;Doussot A;Ebbesen SH;Grandgenett PM;Hollingsworth MA;Jain M;Mallya K;Batra SK;Jarnagin WR;Schwartz RE;Matei I;Peinado H;Stanger BZ;Bromberg J;Lyden D
通讯作者：
Lyden D
DOI：
10.1006/bbrc.1999.2045
发表时间：
2000-01-27
影响因子：
3.1
作者：
El-Husseini, AED;Kwasnicka, D;Vincent, SR
通讯作者：
Vincent, SR
影响因子：
3.7
作者：
Hessvik NP;Sandvig K;Llorente A
通讯作者：
Llorente A
影响因子：
11.2
作者：
Chen G;Kong J;Tucker-Burden C;Anand M;Rong Y;Rahman F;Moreno CS;Van Meir EG;Hadjipanayis CG;Brat DJ
通讯作者：
Brat DJ