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Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation

Vincristine is used in the clinical treatment of colon cancer, especially in patients diagnosed in the advanced phase of cancer development. Unfortunately, similar to other agents used during antitumor therapy, vincristine might induce chemoresistance. Studies of this process focus mainly on the ana...

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Autores principales: Wawro, Marta Ewelina, Sobierajska, Katarzyna, Ciszewski, Wojciech Michał, Niewiarowska, Jolanta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515011/
https://www.ncbi.nlm.nih.gov/pubmed/31010006
http://dx.doi.org/10.3390/ijms20081941
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author Wawro, Marta Ewelina
Sobierajska, Katarzyna
Ciszewski, Wojciech Michał
Niewiarowska, Jolanta
author_facet Wawro, Marta Ewelina
Sobierajska, Katarzyna
Ciszewski, Wojciech Michał
Niewiarowska, Jolanta
author_sort Wawro, Marta Ewelina
collection PubMed
description Vincristine is used in the clinical treatment of colon cancer, especially in patients diagnosed in the advanced phase of cancer development. Unfortunately, similar to other agents used during antitumor therapy, vincristine might induce chemoresistance. Studies of this process focus mainly on the analysis of the molecular mechanisms within cancer, usually ignoring the role of stromal cells. Our present findings confirm that vincristine stimulates the secretion of tumor growth factors class beta and interleukin-6 from cancer-associated fibroblasts as a result of paracrine stimulation by cancer cells. Based on alterations in morphology, modulation of capillary formation, and changes in endothelial and mesenchymal marker profile, our findings demonstrate that higher levels of tumor growth factor-βs and interleukin-6 enhance cancer-associated fibroblast-like cell formation through endothelial–mesenchymal transition and that nonsteroidal anti-inflammatory drug treatment (aspirin and ibuprofen) is able to inhibit this phenomenon. The process appears to be regulated by the rate of microtubule polymerization, depending on β-tubulin composition. While higher levels of tubulin-β2 and tubulin-β4 caused slowed polymerization and reduced the level of factors secreted to the extracellular matrix, tubulin-β3 induced the opposite effect. We conclude that nonsteroidal anti-inflammatory drugs should be considered for use during vincristine monotherapy in the treatment of patients diagnosed with colorectal cancer.
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spelling pubmed-65150112019-05-30 Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation Wawro, Marta Ewelina Sobierajska, Katarzyna Ciszewski, Wojciech Michał Niewiarowska, Jolanta Int J Mol Sci Article Vincristine is used in the clinical treatment of colon cancer, especially in patients diagnosed in the advanced phase of cancer development. Unfortunately, similar to other agents used during antitumor therapy, vincristine might induce chemoresistance. Studies of this process focus mainly on the analysis of the molecular mechanisms within cancer, usually ignoring the role of stromal cells. Our present findings confirm that vincristine stimulates the secretion of tumor growth factors class beta and interleukin-6 from cancer-associated fibroblasts as a result of paracrine stimulation by cancer cells. Based on alterations in morphology, modulation of capillary formation, and changes in endothelial and mesenchymal marker profile, our findings demonstrate that higher levels of tumor growth factor-βs and interleukin-6 enhance cancer-associated fibroblast-like cell formation through endothelial–mesenchymal transition and that nonsteroidal anti-inflammatory drug treatment (aspirin and ibuprofen) is able to inhibit this phenomenon. The process appears to be regulated by the rate of microtubule polymerization, depending on β-tubulin composition. While higher levels of tubulin-β2 and tubulin-β4 caused slowed polymerization and reduced the level of factors secreted to the extracellular matrix, tubulin-β3 induced the opposite effect. We conclude that nonsteroidal anti-inflammatory drugs should be considered for use during vincristine monotherapy in the treatment of patients diagnosed with colorectal cancer. MDPI 2019-04-20 /pmc/articles/PMC6515011/ /pubmed/31010006 http://dx.doi.org/10.3390/ijms20081941 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wawro, Marta Ewelina
Sobierajska, Katarzyna
Ciszewski, Wojciech Michał
Niewiarowska, Jolanta
Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation
title Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation
title_full Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation
title_fullStr Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation
title_full_unstemmed Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation
title_short Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation
title_sort nonsteroidal anti-inflammatory drugs prevent vincristine-dependent cancer-associated fibroblasts formation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515011/
https://www.ncbi.nlm.nih.gov/pubmed/31010006
http://dx.doi.org/10.3390/ijms20081941
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AT niewiarowskajolanta nonsteroidalantiinflammatorydrugspreventvincristinedependentcancerassociatedfibroblastsformation