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Glutamine induces remodeling of tight junctions in Caco-2 colorectal cancer cell
Malignant cells often exhibit significant metabolic alterations, including the utilization of different nutrients to meet energetic and biosynthetic demands. Recent studies have shown that glutamine can support primary colorectal tumor growth and also serve as an alternate energy source during dista...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9718866/ https://www.ncbi.nlm.nih.gov/pubmed/36460896 http://dx.doi.org/10.1007/s12032-022-01896-5 |
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author | Huang, Ching-Ying Chen, Ji-Kai Kuo, Wei-Ting |
author_facet | Huang, Ching-Ying Chen, Ji-Kai Kuo, Wei-Ting |
author_sort | Huang, Ching-Ying |
collection | PubMed |
description | Malignant cells often exhibit significant metabolic alterations, including the utilization of different nutrients to meet energetic and biosynthetic demands. Recent studies have shown that glutamine can support primary colorectal tumor growth and also serve as an alternate energy source during distant metastasis under glucose-limited conditions. However, the overall effects of glutamine on cancer cell physiology are not completely understood. In this study, we investigated how glutamine impacts epithelial integrity in colorectal cancer cells under glucose deprivation. Human colorectal cancer (Caco-2) cells were grown to confluency in transwells and cultured in glucose/pyruvate-free DMEM with various glutamine concentrations (0–50 mM). Cell viability was assessed, and monolayer integrity was examined in terms of transepithelial resistance (TER) and paracellular permeability. Tight junction (TJ) component proteins were examined by immunofluorescence staining and Western blotting. A dose-dependent decrease in TER was observed in Caco-2 cells, but paracellular permeability was not affected after 24 h incubation with glutamine. At the same time, the TJ proteins, zonula occludens (ZO)-1 and Claudin-1, showed lateral undulations and punctate staining patterns accompanied by enlargement of cellular and nuclear sizes. Furthermore, decreased protein levels of ZO-1, but not claudin-1, were found in detergent-insoluble cellular fractions. Notably, the decreased TER and alterations in TJ structure were not associated with cell viability changes. Moreover, the addition of glutamate, which is produced by the first step of glutamine catabolism, had no impact on TER. Our results suggested that the enteral glutamine may play an important role in the regulation of TJ dynamics in colorectal cancer cells. |
format | Online Article Text |
id | pubmed-9718866 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-97188662022-12-04 Glutamine induces remodeling of tight junctions in Caco-2 colorectal cancer cell Huang, Ching-Ying Chen, Ji-Kai Kuo, Wei-Ting Med Oncol Original Paper Malignant cells often exhibit significant metabolic alterations, including the utilization of different nutrients to meet energetic and biosynthetic demands. Recent studies have shown that glutamine can support primary colorectal tumor growth and also serve as an alternate energy source during distant metastasis under glucose-limited conditions. However, the overall effects of glutamine on cancer cell physiology are not completely understood. In this study, we investigated how glutamine impacts epithelial integrity in colorectal cancer cells under glucose deprivation. Human colorectal cancer (Caco-2) cells were grown to confluency in transwells and cultured in glucose/pyruvate-free DMEM with various glutamine concentrations (0–50 mM). Cell viability was assessed, and monolayer integrity was examined in terms of transepithelial resistance (TER) and paracellular permeability. Tight junction (TJ) component proteins were examined by immunofluorescence staining and Western blotting. A dose-dependent decrease in TER was observed in Caco-2 cells, but paracellular permeability was not affected after 24 h incubation with glutamine. At the same time, the TJ proteins, zonula occludens (ZO)-1 and Claudin-1, showed lateral undulations and punctate staining patterns accompanied by enlargement of cellular and nuclear sizes. Furthermore, decreased protein levels of ZO-1, but not claudin-1, were found in detergent-insoluble cellular fractions. Notably, the decreased TER and alterations in TJ structure were not associated with cell viability changes. Moreover, the addition of glutamate, which is produced by the first step of glutamine catabolism, had no impact on TER. Our results suggested that the enteral glutamine may play an important role in the regulation of TJ dynamics in colorectal cancer cells. Springer US 2022-12-02 2023 /pmc/articles/PMC9718866/ /pubmed/36460896 http://dx.doi.org/10.1007/s12032-022-01896-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Paper Huang, Ching-Ying Chen, Ji-Kai Kuo, Wei-Ting Glutamine induces remodeling of tight junctions in Caco-2 colorectal cancer cell |
title | Glutamine induces remodeling of tight junctions in Caco-2 colorectal cancer cell |
title_full | Glutamine induces remodeling of tight junctions in Caco-2 colorectal cancer cell |
title_fullStr | Glutamine induces remodeling of tight junctions in Caco-2 colorectal cancer cell |
title_full_unstemmed | Glutamine induces remodeling of tight junctions in Caco-2 colorectal cancer cell |
title_short | Glutamine induces remodeling of tight junctions in Caco-2 colorectal cancer cell |
title_sort | glutamine induces remodeling of tight junctions in caco-2 colorectal cancer cell |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9718866/ https://www.ncbi.nlm.nih.gov/pubmed/36460896 http://dx.doi.org/10.1007/s12032-022-01896-5 |
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