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Enhanced Vasculogenic Capacity Induced by 5-Fluorouracil Chemoresistance in a Gastric Cancer Cell Line
Chemotherapy is still widely used as a coadjutant in gastric cancer when surgery is not possible or in presence of metastasis. During tumor evolution, gatekeeper mutations provide a selective growth advantage to a subpopulation of cancer cells that become resistant to chemotherapy. When this phenome...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303918/ https://www.ncbi.nlm.nih.gov/pubmed/34299320 http://dx.doi.org/10.3390/ijms22147698 |
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author | Peri, Sara Biagioni, Alessio Versienti, Giampaolo Andreucci, Elena Staderini, Fabio Barbato, Giuseppe Giovannelli, Lisa Coratti, Francesco Schiavone, Nicola Cianchi, Fabio Papucci, Laura Magnelli, Lucia |
author_facet | Peri, Sara Biagioni, Alessio Versienti, Giampaolo Andreucci, Elena Staderini, Fabio Barbato, Giuseppe Giovannelli, Lisa Coratti, Francesco Schiavone, Nicola Cianchi, Fabio Papucci, Laura Magnelli, Lucia |
author_sort | Peri, Sara |
collection | PubMed |
description | Chemotherapy is still widely used as a coadjutant in gastric cancer when surgery is not possible or in presence of metastasis. During tumor evolution, gatekeeper mutations provide a selective growth advantage to a subpopulation of cancer cells that become resistant to chemotherapy. When this phenomenon happens, patients experience tumor recurrence and treatment failure. Even if many chemoresistance mechanisms are known, such as expression of ATP-binding cassette (ABC) transporters, aldehyde dehydrogenase (ALDH1) activity and activation of peculiar intracellular signaling pathways, a common and universal marker for chemoresistant cancer cells has not been identified yet. In this study we subjected the gastric cancer cell line AGS to chronic exposure of 5-fluorouracil, cisplatin or paclitaxel, thus selecting cell subpopulations showing resistance to the different drugs. Such cells showed biological changes; among them, we observed that the acquired chemoresistance to 5-fluorouracil induced an endothelial-like phenotype and increased the capacity to form vessel-like structures. We identified the upregulation of thymidine phosphorylase (TYMP), which is one of the most commonly reported mutated genes leading to 5-fluorouracil resistance, as the cause of such enhanced vasculogenic ability. |
format | Online Article Text |
id | pubmed-8303918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83039182021-07-25 Enhanced Vasculogenic Capacity Induced by 5-Fluorouracil Chemoresistance in a Gastric Cancer Cell Line Peri, Sara Biagioni, Alessio Versienti, Giampaolo Andreucci, Elena Staderini, Fabio Barbato, Giuseppe Giovannelli, Lisa Coratti, Francesco Schiavone, Nicola Cianchi, Fabio Papucci, Laura Magnelli, Lucia Int J Mol Sci Article Chemotherapy is still widely used as a coadjutant in gastric cancer when surgery is not possible or in presence of metastasis. During tumor evolution, gatekeeper mutations provide a selective growth advantage to a subpopulation of cancer cells that become resistant to chemotherapy. When this phenomenon happens, patients experience tumor recurrence and treatment failure. Even if many chemoresistance mechanisms are known, such as expression of ATP-binding cassette (ABC) transporters, aldehyde dehydrogenase (ALDH1) activity and activation of peculiar intracellular signaling pathways, a common and universal marker for chemoresistant cancer cells has not been identified yet. In this study we subjected the gastric cancer cell line AGS to chronic exposure of 5-fluorouracil, cisplatin or paclitaxel, thus selecting cell subpopulations showing resistance to the different drugs. Such cells showed biological changes; among them, we observed that the acquired chemoresistance to 5-fluorouracil induced an endothelial-like phenotype and increased the capacity to form vessel-like structures. We identified the upregulation of thymidine phosphorylase (TYMP), which is one of the most commonly reported mutated genes leading to 5-fluorouracil resistance, as the cause of such enhanced vasculogenic ability. MDPI 2021-07-19 /pmc/articles/PMC8303918/ /pubmed/34299320 http://dx.doi.org/10.3390/ijms22147698 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Peri, Sara Biagioni, Alessio Versienti, Giampaolo Andreucci, Elena Staderini, Fabio Barbato, Giuseppe Giovannelli, Lisa Coratti, Francesco Schiavone, Nicola Cianchi, Fabio Papucci, Laura Magnelli, Lucia Enhanced Vasculogenic Capacity Induced by 5-Fluorouracil Chemoresistance in a Gastric Cancer Cell Line |
title | Enhanced Vasculogenic Capacity Induced by 5-Fluorouracil Chemoresistance in a Gastric Cancer Cell Line |
title_full | Enhanced Vasculogenic Capacity Induced by 5-Fluorouracil Chemoresistance in a Gastric Cancer Cell Line |
title_fullStr | Enhanced Vasculogenic Capacity Induced by 5-Fluorouracil Chemoresistance in a Gastric Cancer Cell Line |
title_full_unstemmed | Enhanced Vasculogenic Capacity Induced by 5-Fluorouracil Chemoresistance in a Gastric Cancer Cell Line |
title_short | Enhanced Vasculogenic Capacity Induced by 5-Fluorouracil Chemoresistance in a Gastric Cancer Cell Line |
title_sort | enhanced vasculogenic capacity induced by 5-fluorouracil chemoresistance in a gastric cancer cell line |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303918/ https://www.ncbi.nlm.nih.gov/pubmed/34299320 http://dx.doi.org/10.3390/ijms22147698 |
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