机构：[1]Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu, China.[2]Center for Clinical Laboratory, the First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu, China.[3]Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou 215004, Jiangsu, China.[4]Department of Oncology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou 215004, Jiangsu, China.
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.
基金：
This work was supported by the National Natural Science Foundation of
China (81572075, 81702080, 81672416, 81702078), the Natural Science
Foundation of the Jiangsu Province (BK20141303, BK20170356), Jiangsu
Province for Outstanding Sci-tech Innovation Team in Colleges and Universities
(SJK2013–10), Jiangsu Province’s Outstanding Medical Academic Leader
and Sci-tech Innovation Team Program (LJ201117), Jiangsu Key Laboratory of
Medical Science and Laboratory Medicine (JSKLM-2014-004), Jiangsu Province’s
Major Project in Research and Development (BE2015667, BE2016717),
the Priority Academic Program Development of Jiangsu Higher Education
Institutions, Special funded projects of national postdoctoral fund
(2017 T100337), Postdoctoral Science Foundation of China (2016 M591791).
Natural science fund for colleges and universities of Jiangsu Province
(17KJB320016), Suzhou Science and Technology Project (SYS201728).
第一作者机构：[1]Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu, China.[2]Center for Clinical Laboratory, the First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu, China.
共同第一作者：
通讯作者：
通讯机构：[1]Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu, China.
推荐引用方式(GB/T 7714)：
Hailong Fu,Huan Yang,Xu Zhang,et al.Exosomal TRIM3 is a novel marker and therapy target for gastric cancer[J].JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH.2018,37(1):162.doi:10.1186/s13046-018-0825-0.
APA：
Hailong Fu,Huan Yang,Xu Zhang,Bo Wang,Jiahui Mao...&Wenrong Xu.(2018).Exosomal TRIM3 is a novel marker and therapy target for gastric cancer.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,37,(1)
MLA：
Hailong Fu,et al."Exosomal TRIM3 is a novel marker and therapy target for gastric cancer".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 37..1(2018):162
医学