The role of extracellular vesicles in phenotypic cancer transformation

Abstract

Background: Cancer has traditionally been considered as a disease resulting from gene mutations. New findings in biology are challenging gene-centered explanations of cancer progression and redirecting them to the non-genetic origins of tumorigenicity. It has become clear that intercellular communication plays a crucial role in cancer progression. Among the most intriguing ways of intercellular communication is that via extracellular vesicles (EVs). EVs are membrane structures released from various types of cells. After separation from the mother membrane, EVs become mobile and may travel from the extracellular space to blood and other body fluids.

Conclusions: Recently it has been shown that tumour cells are particularly prone to vesiculation and that tumour-derived EVs can carry proteins, lipids and nucleic acids causative of cancer progression. The uptake of tumour-derived EVs by noncancerous cells can change their normal phenotype to cancerous. The suppression of vesiculation could slow down tumour growth and the spread of metastases. The purpose of this review is to highlight examples of EV-mediated cancer phenotypic transformation in the light of possible therapeutic applications.

Keywords: cancer progression; exosomes; extracellular vesicles; microvesicles.

FIGURE 1.

Scanning electron micrograph of an isolate from peripheral blood of a healthy human donor (male, 28 years). A mass of extracellular vesicles (arrowhead) and numerous residual erythrocytes (arrow) can be seen. The image was taken using a Quanta TM 250 FEG scanning electron microscope.

FIGURE 2.

A micrograph presenting multiple vesicles budding from a cell of a urothelial cancer cell line T24 labeled with coleratoxin B - FITC. Arrow points to a budding vesicle. The micrograph is a threedimensional reconstruction of optical sections done by a fluorescence microscope.

FIGURE 3.

Formation of extracellular vesicles in tumor cells. A. Budding of plasma membrane. B. Release of exosomes after fusion of multivesicular body with plasma membrane. C. Non-apoptotic blebbing.

FIGURE 4.

Interaction of extracellular vesicles with recipient cell. (A). Adhesion of vesicle molecules to recipient cell surface receptors. (B). Fusion of vesicle with plasma membrane of a recipient cell. (C). Endocytic / phagocytic uptake. D. Extracellular vesicle breakdown and release of its cargo. Transformed cells with pink cytoplasm.

FIGURE 5.

Transfer of oncogenic proteins that induce phenotypic transformation. Tumor cell (pink cytoplasm) with a mutated gene (red nucleus) for membrane protein (EGFRvIII – red asterisk) serve as a donor of this protein which is transferred to a nontumor cell (white cytoplasm). Phenotypic transformation (pink cytoplasm) is induced without mutation (gray nucleus)