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Expression of TXNIP is associated with angiogenesis and postoperative relapse of conventional renal cell carcinoma
One of the common mediator of tumour progression is the oxidative stress induced by inflammatory tumour microenvironment (TME). Activated fibroblasts, local and immune cells produce reactive oxygen species (ROS) supporting tumour cell proliferation and pave the way for metastatic tumour growth. TXNI...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387483/ https://www.ncbi.nlm.nih.gov/pubmed/34433833 http://dx.doi.org/10.1038/s41598-021-96220-y |
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author | Meszaros, Mate Yusenko, Maria Domonkos, Lilla Peterfi, Lehel Kovacs, Gyula Banyai, Daniel |
author_facet | Meszaros, Mate Yusenko, Maria Domonkos, Lilla Peterfi, Lehel Kovacs, Gyula Banyai, Daniel |
author_sort | Meszaros, Mate |
collection | PubMed |
description | One of the common mediator of tumour progression is the oxidative stress induced by inflammatory tumour microenvironment (TME). Activated fibroblasts, local and immune cells produce reactive oxygen species (ROS) supporting tumour cell proliferation and pave the way for metastatic tumour growth. TXNIP regulates ROS generation by inhibiting the antioxidative function of thioredoxin (TXN). The shift of TXNIP/TXN balance towards overexpression of TXNIP is associated with proliferation of endothelial cells during tumor angiogenesis. The oxidative stress activates the hypoxia inducible factor-1 (HIF-1), which plays an important role in the biology of conventional RCC (cRCC). Under oxydative stress TXNIP interacts with NLRP3 inflammasome leading to maturation and secretion of inflammatory cytokine IL1β. To establish the role of TXNIP and downstream genes HIF1α and IL1β in the biology of cRCC, we have applied immunohistochemistry to multi-tissue arrays containing tumours of 691 patients without detectable metastases at the time of operation. We found that cRCC displaying a fine organised capillary network with nuclear translocation of TXNIP and expressing IL1β have a good prognosis. In contrary, we showed a significant correlation between cytoplasmic TXNIP expression, inefficient vascularisation by unorganized and tortuous vessels causing tumour cell necrosis and postoperative tumour relapse of cRCC. |
format | Online Article Text |
id | pubmed-8387483 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-83874832021-09-01 Expression of TXNIP is associated with angiogenesis and postoperative relapse of conventional renal cell carcinoma Meszaros, Mate Yusenko, Maria Domonkos, Lilla Peterfi, Lehel Kovacs, Gyula Banyai, Daniel Sci Rep Article One of the common mediator of tumour progression is the oxidative stress induced by inflammatory tumour microenvironment (TME). Activated fibroblasts, local and immune cells produce reactive oxygen species (ROS) supporting tumour cell proliferation and pave the way for metastatic tumour growth. TXNIP regulates ROS generation by inhibiting the antioxidative function of thioredoxin (TXN). The shift of TXNIP/TXN balance towards overexpression of TXNIP is associated with proliferation of endothelial cells during tumor angiogenesis. The oxidative stress activates the hypoxia inducible factor-1 (HIF-1), which plays an important role in the biology of conventional RCC (cRCC). Under oxydative stress TXNIP interacts with NLRP3 inflammasome leading to maturation and secretion of inflammatory cytokine IL1β. To establish the role of TXNIP and downstream genes HIF1α and IL1β in the biology of cRCC, we have applied immunohistochemistry to multi-tissue arrays containing tumours of 691 patients without detectable metastases at the time of operation. We found that cRCC displaying a fine organised capillary network with nuclear translocation of TXNIP and expressing IL1β have a good prognosis. In contrary, we showed a significant correlation between cytoplasmic TXNIP expression, inefficient vascularisation by unorganized and tortuous vessels causing tumour cell necrosis and postoperative tumour relapse of cRCC. Nature Publishing Group UK 2021-08-25 /pmc/articles/PMC8387483/ /pubmed/34433833 http://dx.doi.org/10.1038/s41598-021-96220-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Meszaros, Mate Yusenko, Maria Domonkos, Lilla Peterfi, Lehel Kovacs, Gyula Banyai, Daniel Expression of TXNIP is associated with angiogenesis and postoperative relapse of conventional renal cell carcinoma |
title | Expression of TXNIP is associated with angiogenesis and postoperative relapse of conventional renal cell carcinoma |
title_full | Expression of TXNIP is associated with angiogenesis and postoperative relapse of conventional renal cell carcinoma |
title_fullStr | Expression of TXNIP is associated with angiogenesis and postoperative relapse of conventional renal cell carcinoma |
title_full_unstemmed | Expression of TXNIP is associated with angiogenesis and postoperative relapse of conventional renal cell carcinoma |
title_short | Expression of TXNIP is associated with angiogenesis and postoperative relapse of conventional renal cell carcinoma |
title_sort | expression of txnip is associated with angiogenesis and postoperative relapse of conventional renal cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387483/ https://www.ncbi.nlm.nih.gov/pubmed/34433833 http://dx.doi.org/10.1038/s41598-021-96220-y |
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