Extracellular vesicle communication pathways as regulatory targets of oncogenic transformation.

Abstract

Pathogenesis of human cancers bridges intracellular oncogenic driver events and their impact on intercellular communication. Among multiple mediators of this 'pathological connectivity' the role of extracellular vesicles (EVs) and their subsets (exosomes, ectosomes, oncosomes) is of particular interest for several reasons. The release of EVs from cancer cells represents a unique mechanism of regulated expulsion of bioactive molecules, a process that also mediates cell-to-cell transfer of lipids, proteins, and nucleic acids. Biological effects of these processes have been implicated in several aspects of cancer-related pathology, including tumour growth, invasion, angiogenesis, metastasis, immunity and thrombosis. Notably, the emerging evidence suggests that oncogenic mutations may impact several aspects of EV-mediated cell-cell communication including: (i) EV release rate and protein content; (ii) molecular composition of cancer EVs; (iii) the inclusion of oncogenic and mutant macromolecules in the EV cargo; (iv) EV-mediated release of genomic DNA; (v) deregulation of mechanisms responsible for EV biogenesis (vesiculome) and (vi) mechanisms of EV uptake by cancer cells. Intriguingly, EV-mediated intercellular transfer of mutant and oncogenic molecules between subpopulations of cancer cells, their indolent counterparts and stroma may exert profound biological effects that often resemble (but are not tantamount to) oncogenic transformation, including changes in cell growth, clonogenicity and angiogenic phenotype, or cause cell stress and death. However, several biological barriers likely curtail a permanent horizontal transformation of normal cells through EV-mediated mechanisms. The ongoing analysis and targeting of EV-mediated intercellular communication pathways can be viewed as a new therapeutic paradigm in cancer, while the analysis of oncogenic cargo contained in EVs released from cancer cells into biofluids is being developed for clinical use as a biomarker and companion diagnostics. Indeed, studies are underway to further explore the multiple links between molecular causality in cancer and various aspects of cellular vesiculation.

• Authors: Dongsic Choi, Tae Hoon Lee, Cristiana Spinelli, Shilpa Chennakrishnaiah, Esterina D'Asti, Janusz Rak
• Journal: Seminars in cell & developmental biology (Semin Cell Dev Biol) Vol. 67 Pg. 11-22 (07 2017) ISSN: 1096-3634 [Electronic] England
• PMID: 28077296 (Publication Type: Journal Article, Review, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• DNA, Neoplasm
• Intercellular Signaling Peptides and Proteins
• Neoplasm Proteins

Topics

• Antineoplastic Agents (therapeutic use)
• Biological Transport (drug effects)
• Cell Communication (drug effects)
• Cell Transformation, Neoplastic (drug effects, genetics, metabolism, pathology)
• DNA, Neoplasm (genetics, metabolism)
• Disease Progression
• Extracellular Vesicles (metabolism, pathology)
• Gene Expression Regulation, Neoplastic
• Humans
• Intercellular Signaling Peptides and Proteins (genetics, metabolism)
• Lymphatic Metastasis
• Neoplasm Proteins (genetics, metabolism)
• Neoplasms (drug therapy, genetics, metabolism, pathology)
• Neovascularization, Pathologic (genetics, metabolism, pathology, prevention & control)
• Oncogenes