Droplet-based microtumor model to assess cell-ECM interactions and drug resistance of gastric cancer cells

Gastric cancer (GC) is a common aggressive malignant tumor with high incidence and mortality worldwide. GC is classified into intestinal and diffuse types according to the histo-morphological features. Because of distinctly different clinico-pathological features, new cancer therapy strategies and i...

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Autores principales: Jang, Minjeong, Koh, Ilkyoo, Lee, Seok Jae, Cheong, Jae-Ho, Kim, Pilnam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269667/
https://www.ncbi.nlm.nih.gov/pubmed/28128310
http://dx.doi.org/10.1038/srep41541
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author Jang, Minjeong
Koh, Ilkyoo
Lee, Seok Jae
Cheong, Jae-Ho
Kim, Pilnam
author_facet Jang, Minjeong
Koh, Ilkyoo
Lee, Seok Jae
Cheong, Jae-Ho
Kim, Pilnam
author_sort Jang, Minjeong
collection PubMed
description Gastric cancer (GC) is a common aggressive malignant tumor with high incidence and mortality worldwide. GC is classified into intestinal and diffuse types according to the histo-morphological features. Because of distinctly different clinico-pathological features, new cancer therapy strategies and in vitro preclinical models for the two pathological variants of GC is necessary. Since extracellular matrix (ECM) influence the biological behavior of tumor cells, we hypothesized that GC might be more similarly modeled in 3D with matrix rather than in 2D. Herein, we developed a microfluidic-based a three-dimensional (3D) in vitro gastric cancer model, with subsequent drug resistance assay. AGS (intestinal type) and Hs746T (diffuse type) gastric cancer cell lines were encapsulated in collagen beads with high cellular viability. AGS exhibited an aggregation pattern with expansive growth, whereas Hs746T showed single-cell-level infiltration. Importantly, in microtumor models, epithelial-mesenchymal transition (EMT) and metastatic genes were upregulated, whereas E-cadherin was downregulated. Expression of ß-catenin was decreased in drug-resistant cells, and chemosensitivity toward the anticancer drug (5-FU) was observed in microtumors. These results suggest that in vitro microtumor models may represent a biologically relevant platform for studying gastric cancer cell biology and tumorigenesis, and for accelerating the development of novel therapeutic targets.
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spelling pubmed-52696672017-02-01 Droplet-based microtumor model to assess cell-ECM interactions and drug resistance of gastric cancer cells Jang, Minjeong Koh, Ilkyoo Lee, Seok Jae Cheong, Jae-Ho Kim, Pilnam Sci Rep Article Gastric cancer (GC) is a common aggressive malignant tumor with high incidence and mortality worldwide. GC is classified into intestinal and diffuse types according to the histo-morphological features. Because of distinctly different clinico-pathological features, new cancer therapy strategies and in vitro preclinical models for the two pathological variants of GC is necessary. Since extracellular matrix (ECM) influence the biological behavior of tumor cells, we hypothesized that GC might be more similarly modeled in 3D with matrix rather than in 2D. Herein, we developed a microfluidic-based a three-dimensional (3D) in vitro gastric cancer model, with subsequent drug resistance assay. AGS (intestinal type) and Hs746T (diffuse type) gastric cancer cell lines were encapsulated in collagen beads with high cellular viability. AGS exhibited an aggregation pattern with expansive growth, whereas Hs746T showed single-cell-level infiltration. Importantly, in microtumor models, epithelial-mesenchymal transition (EMT) and metastatic genes were upregulated, whereas E-cadherin was downregulated. Expression of ß-catenin was decreased in drug-resistant cells, and chemosensitivity toward the anticancer drug (5-FU) was observed in microtumors. These results suggest that in vitro microtumor models may represent a biologically relevant platform for studying gastric cancer cell biology and tumorigenesis, and for accelerating the development of novel therapeutic targets. Nature Publishing Group 2017-01-27 /pmc/articles/PMC5269667/ /pubmed/28128310 http://dx.doi.org/10.1038/srep41541 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Jang, Minjeong
Koh, Ilkyoo
Lee, Seok Jae
Cheong, Jae-Ho
Kim, Pilnam
Droplet-based microtumor model to assess cell-ECM interactions and drug resistance of gastric cancer cells
title Droplet-based microtumor model to assess cell-ECM interactions and drug resistance of gastric cancer cells
title_full Droplet-based microtumor model to assess cell-ECM interactions and drug resistance of gastric cancer cells
title_fullStr Droplet-based microtumor model to assess cell-ECM interactions and drug resistance of gastric cancer cells
title_full_unstemmed Droplet-based microtumor model to assess cell-ECM interactions and drug resistance of gastric cancer cells
title_short Droplet-based microtumor model to assess cell-ECM interactions and drug resistance of gastric cancer cells
title_sort droplet-based microtumor model to assess cell-ecm interactions and drug resistance of gastric cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269667/
https://www.ncbi.nlm.nih.gov/pubmed/28128310
http://dx.doi.org/10.1038/srep41541
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