{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:24:58Z","timestamp":1784053498898,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms22147698","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T10:07:37Z","timestamp":1626689257000},"page":"7698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Enhanced Vasculogenic Capacity Induced by 5-Fluorouracil Chemoresistance in a Gastric Cancer Cell Line"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6698-9582","authenticated-orcid":false,"given":"Sara","family":"Peri","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla, 3-50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6193-7417","authenticated-orcid":false,"given":"Alessio","family":"Biagioni","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, Viale G.B. Morgagni, 50-50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampaolo","family":"Versienti","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, Viale G.B. Morgagni, 50-50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3980-3073","authenticated-orcid":false,"given":"Elena","family":"Andreucci","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, Viale G.B. Morgagni, 50-50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2438-2563","authenticated-orcid":false,"given":"Fabio","family":"Staderini","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla, 3-50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4068-2128","authenticated-orcid":false,"given":"Giuseppe","family":"Barbato","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla, 3-50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4027-4693","authenticated-orcid":false,"given":"Lisa","family":"Giovannelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Children\u2019s Health, University of Florence, Viale Pieraccini, 6-50139 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Coratti","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla, 3-50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Schiavone","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, Viale G.B. Morgagni, 50-50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6936-8693","authenticated-orcid":false,"given":"Fabio","family":"Cianchi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla, 3-50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Papucci","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, Viale G.B. Morgagni, 50-50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4585-1450","authenticated-orcid":false,"given":"Lucia","family":"Magnelli","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, Viale G.B. Morgagni, 50-50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s10555-019-09803-7","article-title":"Update on gastric cancer treatments and gene therapies","volume":"38","author":"Biagioni","year":"2019","journal-title":"Cancer Metastasis Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.3748\/wjg.v22.i11.3069","article-title":"Metastatic gastric cancer treatment: Second line and beyond","volume":"22","author":"Ghosn","year":"2016","journal-title":"World J. 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