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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 May 31

PMID 31141946

Citations 4

Authors

Sara Rocha

Sara Pinto Teles

Mafalda Azevedo

Patricia Oliveira

Joana Carvalho

Carla Oliveira

Affiliations

Soon will be listed here.

Abstract

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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