The Emerging Role of Exosomes in Cancer Chemoresistance.

Jing Li,Wei Liu,Zhengfan Gao,Yong Li,Tianli Fan,Na Gao,Bairen Pang,Xingli Dong

doi:10.3389/fcell.2021.737962

Abstract

Chemoresistance is an impending challenge in cancer treatment. In recent years, exosomes, a subtype of extracellular vesicles with a diameter of 40–150 nm in bloodstream and other bio-fluids, have attracted increasing interest. Exosomes contain proteins, nucleic acids, and lipids, which act as important signaling molecules. Many reports indicate that exosomes play critical roles in chemoresistance through intercellular interactions, including drug removal from cells, transfer of drug resistance phenotypes to other cancer cells, and the increase in plastic stem cell subsets. Exosomes can reflect the physiological and pathological state of parent cells. Owing to their elevated stability, specificity, and sensitivity, exosomes are served as biomarkers in liquid biopsies to monitor cancer chemoresistance, progression, and recurrence. This review summarizes the exosome-mediated mechanisms of cancer chemoresistance, as well as its role in reversing and monitoring chemoresistance. The scientific and technological challenges and future applications of exosomes are also explored.

Highlights

Exosomes are a subclass of heterogeneous extracellular vesicles (EVs) with a diameter of 40–150 nm, which are released from a variety of cells
We focus on discussing the mechanisms of exosome-mediated chemoresistance in cancer, the use of exosomes to reverse chemoresistance, and their application as biomarkers in liquid biopsy to monitor chemoresistance
High expression of exosomal miR92a-3p in serum was found to be closely related to metastasis and chemoresistance in CRC patients; miR-92a-3p in exosomes secreted by cancer-associated fibroblasts (CAFs) is a useful biomarker for monitoring the progression of CRC (Hu et al, 2019)

Summary

Introduction

Several studies have demonstrated that exosomal miRNAs regulate intracellular RNA and protein levels, playing a crucial role in cancer chemoresistance (Patel et al, 2017; Qin et al, 2019). The miRNAs found in exosomes secreted by chemoresistant cancer cells deliver drug-resistant phenotypes to sensitive cancer cells, thereby influencing cell growth and inducing anti-apoptotic processes (Table 2; Chen et al, 2014; Jin et al, 2015; Pink et al, 2015; Weiner-Gorzel et al, 2015; Au et al, 2016; Bouvy et al, 2017; Qin et al, 2017; Wei et al, 2017; Fu et al, 2018; Kanlikilicer et al, 2018; Min et al, 2018; Zhang Y. et al, 2018; Zhu et al, 2019; Han et al, 2020). High expression of exosomal miR92a-3p in serum was found to be closely related to metastasis and chemoresistance in CRC patients; miR-92a-3p in exosomes secreted by CAFs is a useful biomarker for monitoring the progression of CRC (Hu et al, 2019).

Results

Conclusion