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Microenvironment in Disease and Aging

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Front. Cell Dev. Biol. | doi: 10.3389/fcell.2018.00018

Exosome-based cell-cell communication in the tumor microenvironment

  • 1Champalimaud Research, Champalimaud Foundation, Portugal

Tumors are not isolated entities, but complex systemic networks involving cell-cell communication between transformed and non-transformed cells. The milieu created by tumor-associated cells may either support or halt tumor progression. In addition to cell-cell contact, cells communicate through secreted factors via a highly complex system involving characteristics such as ligand concentration, receptor expression and integration of diverse signaling pathways. Of these, extracellular vesicles, such as exosomes, are emerging as novel cell-cell communication mediators in physiological and pathological scenarios. Exosomes, membrane vesicles of endocytic origin released by all cells (both healthy and diseased), ranging in size from 30 to 150nm, transport all the main biomolecules, including lipids, proteins, DNAs, messenger RNAs and microRNA, and perform intercellular transfer of components, locally and systemically. By acting not only in tumor cells, but also in tumor-associated cells such as fibroblasts, endothelium, leukocytes and progenitor cells, tumor- and non-tumor cells-derived exosomes have emerged as new players in tumor growth and invasion, tumor-associated angiogenesis, tissue inflammation and immunologic remodeling. In addition, due to their property of carrying molecules from their cell of origin to the peripheral circulation, exosomes have been increasingly studied as sources of tumor biomarkers in liquid biopsies. Here we review the current literature on the participation of exosomes in the communication between tumor and tumor-associated cells, highlighting the role of this process in the setup of tumor microenvironments that modulate tumor initiation and metastasis.

Keywords: Exosomes, Cancer, Tumor Microenvironment, Extracellular vesicles (EVs), cell-cell communication

Received: 06 Nov 2017; Accepted: 06 Feb 2018.

Edited by:

William C. Hines, University of New Mexico School of Medicine, United States

Reviewed by:

Leonard C. Edelstein, Thomas Jefferson University, United States
Lasse D. Jensen, Linköping University, Sweden  

Copyright: © 2018 Maia, Caja Galán, Strano Moraes, Couto and Costa-Silva. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Bruno Costa-Silva, Champalimaud Foundation, Champalimaud Research, Av. Brasília, Doca de Pedrouços, Lisbon, 1400-038, Lisbon, Portugal,