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...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-04-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/20/8/1941 |
id |
doaj-dcd76a0473864679b031b9d1cce08efb |
---|---|
record_format |
Article |
spelling |
doaj-dcd76a0473864679b031b9d1cce08efb2020-11-24T20:47:30ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-04-01208194110.3390/ijms20081941ijms20081941Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts FormationMarta Ewelina Wawro0Katarzyna Sobierajska1Wojciech Michał Ciszewski2Jolanta Niewiarowska3Department of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, PolandDepartment of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, PolandDepartment of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, PolandDepartment of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, PolandVincristine 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.https://www.mdpi.com/1422-0067/20/8/1941EndMTimmunomodulationCAFscolon cancermicrotubulesIL-6TGF-βsvincristineaspirinibuprofen |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marta Ewelina Wawro Katarzyna Sobierajska Wojciech Michał Ciszewski Jolanta Niewiarowska |
spellingShingle |
Marta Ewelina Wawro Katarzyna Sobierajska Wojciech Michał Ciszewski Jolanta Niewiarowska Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation International Journal of Molecular Sciences EndMT immunomodulation CAFs colon cancer microtubules IL-6 TGF-βs vincristine aspirin ibuprofen |
author_facet |
Marta Ewelina Wawro Katarzyna Sobierajska Wojciech Michał Ciszewski Jolanta Niewiarowska |
author_sort |
Marta Ewelina Wawro |
title |
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_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_sort |
nonsteroidal anti-inflammatory drugs prevent vincristine-dependent cancer-associated fibroblasts formation |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-04-01 |
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. |
topic |
EndMT immunomodulation CAFs colon cancer microtubules IL-6 TGF-βs vincristine aspirin ibuprofen |
url |
https://www.mdpi.com/1422-0067/20/8/1941 |
work_keys_str_mv |
AT martaewelinawawro nonsteroidalantiinflammatorydrugspreventvincristinedependentcancerassociatedfibroblastsformation AT katarzynasobierajska nonsteroidalantiinflammatorydrugspreventvincristinedependentcancerassociatedfibroblastsformation AT wojciechmichałciszewski nonsteroidalantiinflammatorydrugspreventvincristinedependentcancerassociatedfibroblastsformation AT jolantaniewiarowska nonsteroidalantiinflammatorydrugspreventvincristinedependentcancerassociatedfibroblastsformation |
_version_ |
1716809769462792192 |