Enhanced Vasculogenic Capacity Induced by 5-Fluorouracil Chemoresistance in a Gastric Cancer Cell Line
Autor: | Fabio Cianchi, Francesco Coratti, Lucia Magnelli, Giampaolo Versienti, Elena Andreucci, Laura Papucci, Giuseppe Barbato, Sara Peri, Alessio Biagioni, Nicola Schiavone, Fabio Staderini, Lisa Giovannelli |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
medicine.medical_treatment Metastasis 0302 clinical medicine Biology (General) Spectroscopy vasculogenic mimicry Neovascularization Pathologic chemoresistance General Medicine Thalidomide Up-Regulation Computer Science Applications Chemistry 030220 oncology & carcinogenesis Fluorouracil medicine.drug Paclitaxel QH301-705.5 Antineoplastic Agents Article Catalysis epithelial-to-endothelial transition Inorganic Chemistry 03 medical and health sciences Downregulation and upregulation Stomach Neoplasms Cell Line Tumor medicine Humans Vasculogenic mimicry Physical and Theoretical Chemistry Thymidine phosphorylase Molecular Biology QD1-999 Cisplatin Thymidine Phosphorylase Chemotherapy business.industry gastric cancer Organic Chemistry Endothelial Cells Cancer tumor angiogenesis medicine.disease 030104 developmental biology Drug Resistance Neoplasm Cancer cell Cancer research business |
Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 7698, p 7698 (2021) International Journal of Molecular Sciences Volume 22 Issue 14 |
ISSN: | 1661-6596 1422-0067 |
Popis: | 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. |
Databáze: | OpenAIRE |
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