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Open AccessArticle

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

1
i3S–Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
2
Ipatimup—Institute of Molecular Pathology and Immunology of University of Porto, 4200-135 Porto, Portugal
3
ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal
4
Program in Developmental Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
5
Department Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(11), 2608; https://doi.org/10.3390/ijms20112608
Received: 8 April 2019 / Revised: 22 May 2019 / Accepted: 23 May 2019 / Published: 28 May 2019
(This article belongs to the Special Issue Extracellular Vesicles and Metastatic Niche)
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. View Full-Text
Keywords: extracellular vesicles; gastric cancer; epithelial-to-mesenchymal transition; invasion; migration extracellular vesicles; gastric cancer; epithelial-to-mesenchymal transition; invasion; migration
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MDPI and ACS Style

Rocha, S.; Teles, S.P.; Azevedo, M.; Oliveira, P.; Carvalho, J.; Oliveira, C. Gastric Cancer Extracellular Vesicles Tune the Migration and Invasion of Epithelial and Mesenchymal Cells in a Histotype-Dependent Manner. Int. J. Mol. Sci. 2019, 20, 2608. https://doi.org/10.3390/ijms20112608

AMA Style

Rocha S, Teles SP, Azevedo M, Oliveira P, Carvalho J, Oliveira C. Gastric Cancer Extracellular Vesicles Tune the Migration and Invasion of Epithelial and Mesenchymal Cells in a Histotype-Dependent Manner. International Journal of Molecular Sciences. 2019; 20(11):2608. https://doi.org/10.3390/ijms20112608

Chicago/Turabian Style

Rocha, Sara; Teles, Sara P.; Azevedo, Mafalda; Oliveira, Patrícia; Carvalho, Joana; Oliveira, Carla. 2019. "Gastric Cancer Extracellular Vesicles Tune the Migration and Invasion of Epithelial and Mesenchymal Cells in a Histotype-Dependent Manner" Int. J. Mol. Sci. 20, no. 11: 2608. https://doi.org/10.3390/ijms20112608

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