Role of exosomes and exosomal microRNAs in cancer

Abstract

A growing body of evidence indicates that exosomes play a critical role in the cell-cell communication process. Exosomes are biological nanoparticles with an average diameter of 30-100 nm in size and are produced by almost all cell types in the human body; however, cancer cells contain higher concentrations of exosomes than healthy cells. They are released into all body fluids and contain double-stranded DNA (originated from nucleus and mitochondria), a variety of RNA species, and specific protein biomarkers that can be utilized as cancer biomarkers and therapeutic targets, and lipids. Therefore, the specific exosomes secreted by tumor cells could be used to predict the existence of the presence of a tumor in cancer patients. This review summarizes the role of exosomes in cancer development and their potential utility in the clinic.

Keywords: biomarkers; body fluids; cancer; exosomes; extracellular vesicles; miRNA.

Figure 1.. The structure and content of exosome.

Exosomes contain various types of proteins, nucleic acids, lipids and metabolites.

Figure 2.. The formation and releasing of exosome.

(A) Exosome is derived from early endosome formed from plasma membrane. (B) Early endosome becomes late endosomes. (C) Then forms early multivesicular bodies. (D) Late multivesicular bodies. (E) Late multivesicular bodies can either get degraded by lysosomes or fuse with the membrane to release exosomes.

Figure 3.. Exosomes biogenesis and sorting into the blood.

Exosome can be either fused with lysosomes for degradation or with plasma membrane thereby releasing exosomes to the extracellular space. Cell-released exosomes then can be taken up by neighboring recipient cells or travel through biological fluids such as blood, urine or saliva.

Figure 4.. Transfer of exosomal miRNA from donor cell to recipient cells.

(A) miRNAs are sorted to exosome during MVB formation. (B) Exosomes are released into the extracellular space. (C) Exosomal miRNAs can be delivered to recipient cells by endocytosis. (D) Fusion of the exosomes with the plasma membrane using soluble N-ethylmaleimide sensitive fusion into cells primarily uses receptor-mediated endocytosis. (E) Exosomes may also bind to a receptor and activate specific signaling pathways. MVB: Multivesicular body.

Figure 5.. Primary tumor and angiogenesis.

(A) Cell proliferate to form primary tumor formation (without blood vessels). (B) Tumor mass increase and produce angiogenic factors that stimulate new blood vessel formation from the main blood vessel toward the tumor cells.

Figure 6.. Overview of the different exosome isolation and purification techniques.

Figure 7.. The biogenesis of microRNA.

Noncoding miRNAs genes are transcribed in the nucleus into primary miRNAs, which are further processed into premary miRNA and then exported into the cytoplasm where they are finally converted into their matured forms. Mature miRNA then bind to its target mRNA with base pairing, acting as negative regulators of mRNA translation (either mRNA degradation or inhibition of protein expression from mRNA).