Exosomes in gastric cancer: roles, mechanisms, and applications

Abstract

Exosomes are nanosized extracellular vesicles that can be released by almost all types of cells. Initially considered as the garbage bins acting to discard unwanted products of cells, exosomes are now recognized as an important way for cellular communication by transmitting bioactive molecules including proteins, DNA, mRNAs, and non-coding RNAs. The recent studies have shown that exosomes are critically involved in human health and diseases including cancer. Exosomes have been suggested to participate in the promotion of tumorigenesis, tumor growth and metastasis, tumor angiogenesis, tumor immune escape, and tumor therapy resistance. Increasing evidence indicate that exosomes play important roles in gastric cancer development and progression. In this review, we summarized the current understanding of exosomes in gastric cancer with an emphasis on the biological roles of exosomes in gastric cancer and their potential as biomarkers for gastric cancer diagnosis as well as potential targets for gastric cancer therapy.

Keywords: Biomarker; Exosomes; Gastric cancer; Progression; Target.

Fig. 1

The biogenesis and contents of exosomes. The inward budding of the plasma membrane leads to the formation of early endosomes with membrane proteins incorporated. Then the invagination of endosomes and the enclosing of selected cargos including nucleic acids and proteins results in the generation of multivesicular bodies (MVBs), through either ESCRT-dependent or ESCRT-independent mechanisms. Subsequently, these MVBs fuse with plasma membrane and release exosomes into extracellular place. Exosomes release these cargos (proteins, mRNAs, miRNAs, lncRNAs, circRNAs and DNAs) to the recipient cells via mechanisms including a) direct fusion, b) binding with surface proteins, and c) endocytosis

Fig. 2

Roles of tumor cells derived exosomes in GC. Exosomes are critically involved in GC progression including tumorigenesis, metastasis, angiogenesis, immune evasion and drug resistance by transferring functional biomolecules. GC cells derived exosomes can modulate immunity by activating pro-tumor phenotypes of neutrophils and macrophages and inducing the differentiation of T cells to Th17 and Treg cells. GC cells derived exosomes can convert pericytes, fibroblasts and MSCs into myofibroblasts to facilitate tumor angiogenesis and metastasis. Moreover, GC cells derived exosomes can activate endothelial cells to support tumor angiogenesis and promote significant adhesion between mesothelial and GC cells. GC cells derived exosomes can help to create a favorable microenvironment for liver metastasis by acting on liver stromal cells. In addition, pre-adipocytes prefer to differentiate into brown-like type by GC cells derived exosomes