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      Vesicle-Mediated Control of Cell Function: The Role of Extracellular Matrix and Microenvironment

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          Abstract

          Extracellular vesicles (EVs) — including exosomes, microvesicles and apoptotic bodies — have received much scientific attention last decade as mediators of a newly discovered cell-to-cell communication system, acting at short and long distances. EVs carry biologically active molecules, thus providing signals that influence a spectrum of functions in recipient cells during various physiological and pathological processes. Recent findings point to EVs as very attractive immunomodulatory therapeutic agents, vehicles for drug delivery and diagnostic and prognostic biomarkers in liquid biopsies. In addition, EVs interact with and regulate the synthesis of extracellular matrix (ECM) components, which is crucial for organ development and wound healing, as well as bone and cardiovascular calcification. EVs carrying matrix metalloproteinases (MMPs) are involved in ECM remodeling, thus modifying tumor microenvironment and contributing to premetastatic niche formation and angiogenesis. Here we review the role of EVs in control of cell function, with emphasis on their interaction with ECM and microenvironment in health and disease.

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          Most cited references82

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          Microenvironmental regulation of metastasis.

          Metastasis is a multistage process that requires cancer cells to escape from the primary tumour, survive in the circulation, seed at distant sites and grow. Each of these processes involves rate-limiting steps that are influenced by non-malignant cells of the tumour microenvironment. Many of these cells are derived from the bone marrow, particularly the myeloid lineage, and are recruited by cancer cells to enhance their survival, growth, invasion and dissemination. This Review describes experimental data demonstrating the role of the microenvironment in metastasis, identifies areas for future research and suggests possible new therapeutic avenues.
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            Liver regeneration.

            Liver regeneration after partial hepatectomy is a very complex and well-orchestrated phenomenon. It is carried out by the participation of all mature liver cell types. The process is associated with signaling cascades involving growth factors, cytokines, matrix remodeling, and several feedbacks of stimulation and inhibition of growth related signals. Liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. In situations when hepatocytes or biliary cells are blocked from regeneration, these cell types can function as facultative stem cells for each other.
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              Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis.

              Exosomes are naturally occurring biological nanovesicles utilized by tumors to communicate signals to local and remote cells and tissues. Melanoma exosomes can incite a proangiogenic signaling program capable of remodeling tissue matrices. In this study, we show exosome-mediated conditioning of lymph nodes and define microanatomic responses that license metastasis of melanoma cells. Homing of melanoma exosomes to sentinel lymph nodes imposes synchronized molecular signals that effect melanoma cell recruitment, extracellular matrix deposition, and vascular proliferation in the lymph nodes. Our findings highlight the pathophysiologic role and mechanisms of an exosome-mediated process of microanatomic niche preparation that facilitates lymphatic metastasis by cancer cells.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                05 June 2018
                2018
                : 9
                : 651
                Affiliations
                [1] 1IMDEA Nanoscience Institute , Madrid, Spain
                [2] 2Fundación de Investigación HM Hospitales , Madrid, Spain
                [3] 3Facultad de Medicina (IMMA), Universidad CEU San Pablo , Madrid, Spain
                Author notes

                Edited by: Giancarlo Forte, International Clinical Research Center (FNUSA-ICRC), Czechia

                Reviewed by: Wolfgang Holnthoner, Ludwig Boltzmann Gesellschaft (LBG), Austria; Rosemary Wangensteen, Universidad de Jaén, Spain

                *Correspondence: Gorjana, Rackov gorjanarackov@ 123456gmail.com Angel Ayuso-Sacido, ayusosacido@ 123456gmail.com

                These authors have contributed equally to this work.

                This article was submitted to Integrative Physiology, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2018.00651
                5996101
                29922170
                9d3f5f66-2dae-4efb-b1a4-20a73a7cb840
                Copyright © 2018 Rackov, Garcia-Romero, Esteban-Rubio, Carrión-Navarro, Belda-Iniesta and Ayuso-Sacido.

                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.

                History
                : 31 March 2018
                : 14 May 2018
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 119, Pages: 12, Words: 0
                Categories
                Physiology
                Review

                Anatomy & Physiology
                extracellular vesicles,exosomes,extracellular matrix,microenvironment,cell function

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