Exosomes: key players in cancer and potential therapeutic strategy

Abstract

Exosomes are extracellular vesicles secreted by most eukaryotic cells and participate in intercellular communication. The components of exosomes, including proteins, DNA, mRNA, microRNA, long noncoding RNA, circular RNA, etc., which play a crucial role in regulating tumor growth, metastasis, and angiogenesis in the process of cancer development, and can be used as a prognostic marker and/or grading basis for tumor patients. Hereby, we mainly summarized as followed: the role of exosome contents in cancer, focusing on proteins and noncoding RNA; the interaction between exosomes and tumor microenvironment; the mechanisms that epithelial-mesenchymal transition, invasion and migration of tumor affected by exosomes; and tumor suppression strategies based on exosomes. Finally, the application potential of exosomes in clinical tumor diagnosis and therapy is prospected, which providing theoretical supports for using exosomes to serve precise tumor treatment in the clinic.

Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment

“…Collectively, exosomes can cause tumor cells to acquire resistance by various pathways, including the reduction of intracellular drug concentrations, induction of EMT, activation of anti-apoptotic pathways, alteration of critical survival signal transduction pathways, and modulation of the immune system ( Mashouri et al, 2019 ; Steinbichler et al, 2019 ; Dai et al, 2020 ).…”

Current Status of Circulating Tumor Cells, Circulating Tumor DNA, and Exosomes in Breast Cancer Liquid Biopsies

“…These are microvesicles (also referred to as ectosomes) of 100–1000 nm that are formed by plasma membrane shedding, and exosomes of 30–150 nm that derive from the endocytic pathway and are released when multivesicular bodies (MVBs) fuse with the plasma membrane [ 92 , 93 ]. Exosomes, in particular, have gained substantial attention over the last few years as experimental evidence has demonstrated that they contribute to the development and progression of human diseases, including cancer [ 92 , 94 , 95 ]. It has been demonstrated that cancer cells release more exosomes compared to normal cells as a response to pathophysiological conditions like hypoxia and low pH in the tumor microenvironment or to oncogenic activities within the cells [ 96 , 97 , 98 ].…”

“…Importantly, exosomes are also detected in body fluids, including blood, suggesting that they can act as mediators of long-distance cellular signaling [ 99 , 100 , 101 ]. In cancer, exosomes may promote tumor cell migration, invasion, and formation of distant metastatic niches [ 92 , 94 , 98 ]. They have also been shown to play a role in cancer cell immune evasion [ 102 ].…”

Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis

“…Likewise, exosomal miR-106b-3p is abundantly detected in the serum of metastatic colorectal cancer patients, induces tumor cell migration, invasion and epithelial-to-mesenchymal transition (EMT), and correlates with poor survival [ 69 , 70 ]. Other pro-invasive factors transported via tumor-released EVs include TGF-β, caveolin-1, HIF1α and β-catenin, all of which were shown to promote EMT, extracellular matrix remodeling and metastatic niche formation [ 71 ]. Examples come from multiple cancer types: colorectal cancer, where EVs transfer mutated β-catenin to modulate Wnt signaling and enhance tumor growth [ 72 ]; gastric cancer, where EV-mediated TGF-β transfer and subsequent activation of the TGF-β/Smad pathway assists in the formation of metastatic niches [ 73 ]; and nasopharyngeal carcinoma, where EVs with enhanced levels of HIF1α increase the migration and invasion of tumor cells [ 74 ].…”