{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T07:01:00Z","timestamp":1791961260369,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,4,20]],"date-time":"2019-04-20T00:00:00Z","timestamp":1555718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005632","name":"Narodowe Centrum Bada\u0144 i Rozwoju","doi-asserted-by":"publisher","award":["Pol-Nor\/209521\/5\/2013"],"award-info":[{"award-number":["Pol-Nor\/209521\/5\/2013"]}],"id":[{"id":"10.13039\/501100005632","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2017\/26\/D\/NZ7\/00633"],"award-info":[{"award-number":["2017\/26\/D\/NZ7\/00633"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005888","name":"Uniwersytet Medyczny w Lodzi","doi-asserted-by":"publisher","award":["502-03\/6-171-02\/502-64-120"],"award-info":[{"award-number":["502-03\/6-171-02\/502-64-120"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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-\u03b2s and interleukin-6 enhance cancer-associated fibroblast-like cell formation through endothelial\u2013mesenchymal 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 \u03b2-tubulin composition. While higher levels of tubulin-\u03b22 and tubulin-\u03b24 caused slowed polymerization and reduced the level of factors secreted to the extracellular matrix, tubulin-\u03b23 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.<\/jats:p>","DOI":"10.3390\/ijms20081941","type":"journal-article","created":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T11:02:53Z","timestamp":1555930973000},"page":"1941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8327-5277","authenticated-orcid":false,"given":"Marta Ewelina","family":"Wawro","sequence":"first","affiliation":[{"name":"Department of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6\/8, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3510-0098","authenticated-orcid":false,"given":"Katarzyna","family":"Sobierajska","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6\/8, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6251-6043","authenticated-orcid":false,"given":"Wojciech Micha\u0142","family":"Ciszewski","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6\/8, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0561-7766","authenticated-orcid":false,"given":"Jolanta","family":"Niewiarowska","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6\/8, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1475-2867-14-41","article-title":"The role of cancer-associated fibroblasts, solid stress and other microenvironmental factors in tumor progression and therapy resistance","volume":"14","author":"Kharaishvili","year":"2014","journal-title":"Cancer Cell Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9608","DOI":"10.18632\/oncotarget.14155","article-title":"The tumor microenvironment promotes cancer progression and cell migration","volume":"8","author":"Salvatore","year":"2017","journal-title":"Oncotarget"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10123","DOI":"10.1158\/0008-5472.CAN-07-3127","article-title":"Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts","volume":"67","author":"Zeisberg","year":"2007","journal-title":"Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.3390\/cancers7040902","article-title":"Cancer-associated fibroblasts: Their characteristics and their roles in tumor growth","volume":"7","author":"Shiga","year":"2015","journal-title":"Cancers"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/bjc.2013.748","article-title":"Interleukin-6 released by colon cancer-associated fibroblasts is critical for tumour angiogenesis: Anti-interleukin-6 receptor antibody suppressed angiogenesis and inhibited tumour\u2013stroma interaction","volume":"110","author":"Nagasaki","year":"2014","journal-title":"Br. 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