Exosome: Function and Role in Cancer Metastasis and Drug Resistance

Abstract

As a kind of nanometric lipidic vesicles, exosomes have been presumed to play a leading role in the regulation of tumor microenvironment through exosomes-mediated transfer of proteins and genetic materials. Tumor-derived exosomes are recognized as a critical determinant of the tumor progression. Intriguingly, some current observations have identified that exosomes are essential for several intercellular exchanges of proteins, messenger RNAs, noncoding RNAs (including long noncoding RNAs and microRNAs) as well as to the process of cancer metastasis and drug resistance. Herein, we review the role of exosomes and their molecular cargos in cancer invasion and metastasis, summarize how they interact with antitumor agents, and highlight their translational implications.

Keywords: Exosomes; cancer; contents; drug resistance; metastasis.

Figure 1.

Generation and the structure of exosome. Exosomes are vesicles with a phospholipid bilayer membrane; they are considered to be secreted from intracellular multivesicular bodies (MVBs or late endosomes) into extracellular space. The exosomes contain a range of proteins, RNAs, mRNAs, and DNA molecular cargoes, with surface protein markers including CD9, CD63, CD81, TSG101, and ALIX, and there are equal or asymmetrical distributions of phospholipids between the 2 leaflets of exosome membrane. mRNAs indicates messenger RNAs; TBS, Tris-buffered saline; TSG101, tumor-susceptibility gene-101; ALG-2-interacting protein X (ALIX).

Figure 2.

Regulating network of exosomal proteins and ncRNAs in tumors. Molecular signaling of exosomal nc-RNAs (ie, exosomal miRNAs [exo-miRNAs] and exosomal lncRNAs [exo-lncRNAs]) and proteins in most frequent cancer-related pathways involved in cancer metastasis (ie, EMT, TGF-β, and Wnt). These bioactive molecules carried in exosomes take effects in metastasis promotion or repression and interact with others. EMT pathway is a process by which epithelial cells lose their cell–cell adhesion and acquire migratory property to become mesenchymal stem cells; TGF-β pathway is involved in cellular processes including cell growth, differentiation, and invasion; and Wnt pathway regulates crucial aspects of cell fate determination and cell migration during embryonic development. ncRNAs indicates noncoding RNAs; miRNA, microRNA; lncRNAs, long noncoding RNAs; EMT, epithelial–mesenchymal transition; TGF-β, transforming growth factor β.