Abstract
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.
Highlights
Exosomes are critically involved in cancer development and progression
The results showed that the expression of Tripartite motif-containing 3 (TRIM3) in exosomes from the serum of gastric cancer patients was much lower than that from the healthy controls, which was further confirmed by western blot assay (Fig. 2b)
We found that the concentration of exosomes from the serum of gastric cancer patients was higher than that from the healthy controls, which is consistent with that reported in the other cancers, suggesting that the increased level of exosomes is an important indicator of cancer progression
Summary
Exosomes are critically involved in cancer development and progression. The exosomal contents have been suggested as ideal cancer biomarkers. It is estimated that there are approximately 750,000 new cases diagnosed annually around the world, and 5-year overall survival rates are less than 25% [1]. In spite of the progress in chemotherapy, radiotherapy and surgical techniques for GC in recent years, the survival rate of GC patients remains unsatisfactory [2]. Exosomes are generated from the internal vesicles of multivesicular bodies (MVBs), which release their contents into biological fluids [5, 6]. Exosomes in the body fluids such as blood and urine could serve as diagnostic markers for various diseases including cancer because they may reflect the pathological state of their derived cells [7,8,9].
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