Exosomal TRIM3 is a novel marker and therapy target for gastric cancer

被引：108
作者：
Fu, Hailong [1 ,2 ]
Yang, Huan [1 ,3 ]
Zhang, Xu [1 ]
Wang, Bo [4 ]
Mao, Jiahui [1 ]
Li, Xia [1 ]
Wang, Mei [1 ]
Zhang, Bin [1 ]
Sun, Zixuan [1 ]
Qian, Hui [1 ]
Xu, Wenrong [1 ]
机构：
[1] Jiangsu Univ, Sch Med, Jiangsu Key Lab Med Sci & Lab Med, 301 Xuefu Rd, Zhenjiang 212013, Jiangsu, Peoples R China
[2] Soochow Univ, Affiliated Hosp 1, Ctr Clin Lab, 188 Shizi St, Suzhou 215006, Jiangsu, Peoples R China
[3] Soochow Univ, Affiliated Hosp 2, Dept Clin Lab, 1055 Sanxiang Rd, Suzhou 215004, Jiangsu, Peoples R China
[4] Soochow Univ, Affiliated Hosp 2, Dept Oncol, 1055 Sanxiang Rd, Suzhou 215004, Jiangsu, Peoples R China
来源：
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | 2018年 / 37卷
基金：
中国国家自然科学基金;
关键词：
Gastric cancer; Exosomes; TRIM3; Progression; Diagnosis; Therapy; PROMOTE TUMOR-GROWTH; RING FINGER PROTEIN; DIAGNOSTIC BIOMARKERS; COLORECTAL-CANCER; PANCREATIC-CANCER; CELL-FUNCTION; MICROVESICLES; SUPPRESSOR; MELANOMA; GLIOBLASTOMA;
D O I：
10.1186/s13046-018-0825-0
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
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页数：16
相关论文
共 42 条
[1]   Exosomal HIF1α supports invasive potential of nasopharyngeal carcinoma-associated LMP1-positive exosomes [J].
Aga, M. ;
Bentz, G. L. ;
Raffa, S. ;
Torrisi, M. R. ;
Kondo, S. ;
Wakisaka, N. ;
Yoshizaki, T. ;
Pagano, J. S. ;
Shackelford, J. .
ONCOGENE, 2014, 33 (37) :4613-4622
[2]   Intercellular transfer of the oncogenic receptor EGFrvIII by microvesicles derived from tumour cells [J].
Al-Nedawi, Khalid ;
Meehan, Brian ;
Micallef, Johann ;
Lhotak, Vladimir ;
May, Linda ;
Guha, Abhijit ;
Rak, Janusz .
NATURE CELL BIOLOGY, 2008, 10 (05) :619-U24
[3]   Proteomic analysis of exosomes isolated from human malignant pleural effusions [J].
Bard, MP ;
Hegmans, JP ;
Hemmes, A ;
Luider, TM ;
Willemsen, R ;
Severijnen, LAA ;
van Meerbeeck, JP ;
Burgers, SA ;
Hoogsteden, HC ;
Lambrecht, BN .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2004, 31 (01) :114-121
[4]   Exosomes in bodily fluids are a highly stable resource of disease biomarkers [J].
Boukouris, Stephanie ;
Mathivanan, Suresh .
PROTEOMICS CLINICAL APPLICATIONS, 2015, 9 (3-4) :358-367
[5]   Loss of heterozygosity of TRIM3 in malignant gliomas [J].
Boulay, Jean-Louis ;
Stiefel, Urs ;
Taylor, Elisabeth ;
Dolder, Beatrice ;
Merlo, Adrian ;
Hirth, Frank .
BMC CANCER, 2009, 9
[6]  
Cambiaghi V, 2012, ADV EXP MED BIOL, V770, P77
[7]   Decreased expression of TRIM3 is associated with poor prognosis in patients with primary hepatocellular carcinoma [J].
Chao, Jie ;
Zhang, Xiao-Fei ;
Pan, Qiu-Zhong ;
Zhao, Jing-Jing ;
Jiang, Shan-Shan ;
Wang, Ying ;
Zhang, Jian-Hua ;
Xia, Jian-Chuan .
MEDICAL ONCOLOGY, 2014, 31 (08)
[8]   Human Brat Ortholog TRIM3 Is a Tumor Suppressor That Regulates Asymmetric Cell Division in Glioblastoma [J].
Chen, Gang ;
Kong, Jun ;
Tucker-Burden, Carol ;
Anand, Monika ;
Rong, Yuan ;
Rahman, Fahmia ;
Moreno, Carlos S. ;
Van Meir, Erwin G. ;
Hadjipanayis, Constantinos G. ;
Brat, Daniel J. .
CANCER RESEARCH, 2014, 74 (16) :4536-4548
[9]   Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver [J].
Costa-Silva, Bruno ;
Aiello, Nicole M. ;
Ocean, Allyson J. ;
Singh, Swarnima ;
Zhang, Haiying ;
Thakur, Basant Kumar ;
Becker, Annette ;
Hoshino, Ayuko ;
Mark, Milica Tesic ;
Molina, Henrik ;
Xiang, Jenny ;
Zhang, Tuo ;
Theilen, Till-Martin ;
Garcia-Santos, Guillermo ;
Williams, Caitlin ;
Ararso, Yonathan ;
Huang, Yujie ;
Rodrigues, Goncalo ;
Shen, Tang-Long ;
Labori, Knut Jorgen ;
Lothe, Inger Marie Bowitz ;
Kure, Elm H. ;
Hernandez, Jonathan ;
Doussot, Alexandre ;
Ebbesen, Saya H. ;
Grandgenett, Paul M. ;
Hollingsworth, Michael A. ;
Jain, Maneesh ;
Mallya, Kavita ;
Batra, Surinder K. ;
Jarnagin, William R. ;
Schwartz, Robert E. ;
Matei, Irina ;
Peinado, Hector ;
Stanger, Ben Z. ;
Bromberg, Jacqueline ;
Lyden, David .
NATURE CELL BIOLOGY, 2015, 17 (06) :816-+
[10]  
Derisory B. M., 2013, MOL CELL PROTEOMICS, V12, P343, DOI DOI 10.1074/MCP.M112.022806
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