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Gastric Cancer Extracellular Vesicles Tune the Migration and Invasion of Epithelial and Mesenchymal Cells in a Histotype-Dependent Manner

Extracellular vesicles (EVs) secreted by tumor cells modulate recipient cells’ behavior, but their effects in normal cells from the tumor microenvironment remain poorly known. In this study, we dissected the functional impact of gastric cancer cell-derived EVs (GC-EVs), representative of distinct GC...

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Autores principales: Rocha, Sara, Teles, Sara Pinto, Azevedo, Mafalda, Oliveira, Patrícia, Carvalho, Joana, Oliveira, Carla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600627/
https://www.ncbi.nlm.nih.gov/pubmed/31141946
http://dx.doi.org/10.3390/ijms20112608
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author Rocha, Sara
Teles, Sara Pinto
Azevedo, Mafalda
Oliveira, Patrícia
Carvalho, Joana
Oliveira, Carla
author_facet Rocha, Sara
Teles, Sara Pinto
Azevedo, Mafalda
Oliveira, Patrícia
Carvalho, Joana
Oliveira, Carla
author_sort Rocha, Sara
collection PubMed
description Extracellular vesicles (EVs) secreted by tumor cells modulate recipient cells’ behavior, but their effects in normal cells from the tumor microenvironment remain poorly known. In this study, we dissected the functional impact of gastric cancer cell-derived EVs (GC-EVs), representative of distinct GC histotypes, on the behavior of normal isogenic epithelial and mesenchymal cells. GC-EVs were isolated by differential centrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and imaging flow-cytometry. Epithelial and mesenchymal cells were challenged with GC-EVs and submitted to proliferation, migration, and invasion assays. Expression of epithelial and mesenchymal markers was followed by immunofluorescence and flow-cytometry. Our results indicated that GC-EVs secreted by diffuse-type cancer cells decrease the migration of recipient cells. This effect was more prominent and persistent for mesenchymal recipient cells, which also increased Fibronectin expression in response to EVs. GC-EVs secreted by cancer cells derived from tumors with an intestinal component increased invasion of recipient epithelial cells, without changes in EMT markers. In summary, this study demonstrated that GC-EVs modulate the migration and invasion of epithelial and mesenchymal cells from the tumor microenvironment, in a histotype-dependent manner, highlighting new features of intestinal and diffuse-type GC cells, which may help explaining differential metastasis patterns and aggressiveness of GC histotypes.
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spelling pubmed-66006272019-07-16 Gastric Cancer Extracellular Vesicles Tune the Migration and Invasion of Epithelial and Mesenchymal Cells in a Histotype-Dependent Manner Rocha, Sara Teles, Sara Pinto Azevedo, Mafalda Oliveira, Patrícia Carvalho, Joana Oliveira, Carla Int J Mol Sci Article Extracellular vesicles (EVs) secreted by tumor cells modulate recipient cells’ behavior, but their effects in normal cells from the tumor microenvironment remain poorly known. In this study, we dissected the functional impact of gastric cancer cell-derived EVs (GC-EVs), representative of distinct GC histotypes, on the behavior of normal isogenic epithelial and mesenchymal cells. GC-EVs were isolated by differential centrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and imaging flow-cytometry. Epithelial and mesenchymal cells were challenged with GC-EVs and submitted to proliferation, migration, and invasion assays. Expression of epithelial and mesenchymal markers was followed by immunofluorescence and flow-cytometry. Our results indicated that GC-EVs secreted by diffuse-type cancer cells decrease the migration of recipient cells. This effect was more prominent and persistent for mesenchymal recipient cells, which also increased Fibronectin expression in response to EVs. GC-EVs secreted by cancer cells derived from tumors with an intestinal component increased invasion of recipient epithelial cells, without changes in EMT markers. In summary, this study demonstrated that GC-EVs modulate the migration and invasion of epithelial and mesenchymal cells from the tumor microenvironment, in a histotype-dependent manner, highlighting new features of intestinal and diffuse-type GC cells, which may help explaining differential metastasis patterns and aggressiveness of GC histotypes. MDPI 2019-05-28 /pmc/articles/PMC6600627/ /pubmed/31141946 http://dx.doi.org/10.3390/ijms20112608 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rocha, Sara
Teles, Sara Pinto
Azevedo, Mafalda
Oliveira, Patrícia
Carvalho, Joana
Oliveira, Carla
Gastric Cancer Extracellular Vesicles Tune the Migration and Invasion of Epithelial and Mesenchymal Cells in a Histotype-Dependent Manner
title Gastric Cancer Extracellular Vesicles Tune the Migration and Invasion of Epithelial and Mesenchymal Cells in a Histotype-Dependent Manner
title_full Gastric Cancer Extracellular Vesicles Tune the Migration and Invasion of Epithelial and Mesenchymal Cells in a Histotype-Dependent Manner
title_fullStr Gastric Cancer Extracellular Vesicles Tune the Migration and Invasion of Epithelial and Mesenchymal Cells in a Histotype-Dependent Manner
title_full_unstemmed Gastric Cancer Extracellular Vesicles Tune the Migration and Invasion of Epithelial and Mesenchymal Cells in a Histotype-Dependent Manner
title_short Gastric Cancer Extracellular Vesicles Tune the Migration and Invasion of Epithelial and Mesenchymal Cells in a Histotype-Dependent Manner
title_sort gastric cancer extracellular vesicles tune the migration and invasion of epithelial and mesenchymal cells in a histotype-dependent manner
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600627/
https://www.ncbi.nlm.nih.gov/pubmed/31141946
http://dx.doi.org/10.3390/ijms20112608
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