Small Extracellular Vesicles: Key Forces Mediating the Development and Metastasis of Colorectal Cancer

Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide, and its incidence and mortality rates have been increasing annually in recent years. A variety of different small extracellular vesicles (sEVs) are important mediators of intercellular communication and have an important role in tumor metastasis and progression. The development and metastasis of CRC are closely linked to tumor-cell-derived sEVs, non-tumor-cell-derived sEVs, and intestinal-microbiota-derived sEVs. Numerous studies have shown that the tumor microenvironment (TME) is a key component in the regulation of CRC proliferation, development, and metastasis. These sEVs can create a TME conducive to CRC growth and metastasis by forming an immunosuppressive microenvironment, remodeling the extracellular matrix, and promoting tumor cell metabolism. Therefore, in this paper, we review the role of different types of sEVs in colorectal cancer development and metastasis. Furthermore, based on the properties of sEVs, we further discuss the use of sEVs as early biomarkers for colorectal cancer diagnosis and the potential for their use in the treatment of CRC.

Small Extracellular Vesicles (sEVs) Biogenesis Molecular Players Are Associated with Clinical Outcome of Colorectal Cancer Patients

“…The significant role of sEVs in CRC initiation and progression has been confirmed with numerous published studies. Many studies have shed light on the mechanisms through which sEVs are implicated in CRC development and progression [ 23 ]. However, limited data are available, regarding the clinical significance of key molecules related to the exosomal biogenesis.…”

“…Plasma exosomes are a pool of sEVs derived from different cells. However, it is known that tumor-derived sEVs have the potential to function mainly locally reshaping the tumor microenvironment towards to a more immunosuppressive state, by remodeling the extracellular matrix and promoting tumor cell metabolism, growth, and metastasis [ 23 ]. Therefore, this lack of correlation between gene expression and tumor-derived plasma exosome concentrations may reflects the mechanism through which cancer-derived sEVs affect CRC (mainly locally) and not the absence of impact in pathophysiological level.…”

A New Potential Therapeutic Target for Cancer in Ubiquitin-Like Proteins—UBL3

“…The exosome is an sEV, defined by sizes of 30–150 nm in diameter. The roles of sEVs have been discussed in the context of progression and metastasis in various cancers [ 8 , 9 , 10 ]. sEVs are capable of transporting molecular cargo from one cell to another through vascular vessels and intercellular spaces.…”

Cancer-Derived Extracellular Vesicles as Biomarkers for Cutaneous Squamous Cell Carcinoma: A Systematic Review

“…Their potential as biomarkers for hepatocellular carcinoma (HCC), various pediatric solid tumors, pancreatic, ovarian, and bladder cancer has been shown in preliminary research [ 22 , 23 , 24 , 25 ]. Others have used EVs as prognostic indicators for colorectal cancer, breast cancer, and HCC [ 22 , 26 , 27 ]. More advanced applications of EVs include prediction and monitoring of treatment response as well as therapeutic cargos [ 28 , 29 , 30 , 31 ].…”