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Grainyhead-Like 3 Influences Migration and Invasion of Urothelial Carcinoma Cells

Invasive urothelial carcinomas of the bladder (UCB) characteristically show a loss of differentiation markers. The transcription factor Grainyhead-like 3 (GRHL3) plays an important role in the development and differentiation of normal urothelium. The contribution to UCB progression is still elusive....

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Autores principales: Wezel, Felix, Lustig, Johannes, Azoitei, Anca, Liu, Junnan, Meessen, Sabine, Najjar, Gregoire, Zehe, Viktor, Faustmann, Philipp, Zengerling, Friedemann, John, Axel, Martini, Thomas, Bolenz, Christian, Günes, Cagatay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000182/
https://www.ncbi.nlm.nih.gov/pubmed/33803949
http://dx.doi.org/10.3390/ijms22062959
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author Wezel, Felix
Lustig, Johannes
Azoitei, Anca
Liu, Junnan
Meessen, Sabine
Najjar, Gregoire
Zehe, Viktor
Faustmann, Philipp
Zengerling, Friedemann
John, Axel
Martini, Thomas
Bolenz, Christian
Günes, Cagatay
author_facet Wezel, Felix
Lustig, Johannes
Azoitei, Anca
Liu, Junnan
Meessen, Sabine
Najjar, Gregoire
Zehe, Viktor
Faustmann, Philipp
Zengerling, Friedemann
John, Axel
Martini, Thomas
Bolenz, Christian
Günes, Cagatay
author_sort Wezel, Felix
collection PubMed
description Invasive urothelial carcinomas of the bladder (UCB) characteristically show a loss of differentiation markers. The transcription factor Grainyhead-like 3 (GRHL3) plays an important role in the development and differentiation of normal urothelium. The contribution to UCB progression is still elusive. Differential expression of GRHL3 was assessed in normal human urothelium and in non-invasive and invasive bladder cancer cell lines. The contribution of GRHL3 to cell proliferation, viability and invasion in UCB cell lines was determined by gain- and loss-of-function assays in vitro and in an organ culture model using de-epithelialized porcine bladders. GRHL3 expression was detectable in normal human urothelial cells and showed significantly higher mRNA and protein levels in well-differentiated, non-invasive RT4 urothelial carcinoma cells compared to moderately differentiated RT112 cells. GRHL3 expression was absent in anaplastic and invasive T24 cells. Ectopic de novo expression of GRHL3 in T24 cells significantly impaired their migration and invasion properties in vitro and in organ culture. Its downregulation improved the invasive capacity of RT4 cells. The results indicate that GRHL3 may play a role in progression and metastasis in UCB. In addition, this work demonstrates that de-epithelialized porcine bladder organ culture can be a useful, standardized tool to assess the invasive capacity of cancer cells.
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spelling pubmed-80001822021-03-28 Grainyhead-Like 3 Influences Migration and Invasion of Urothelial Carcinoma Cells Wezel, Felix Lustig, Johannes Azoitei, Anca Liu, Junnan Meessen, Sabine Najjar, Gregoire Zehe, Viktor Faustmann, Philipp Zengerling, Friedemann John, Axel Martini, Thomas Bolenz, Christian Günes, Cagatay Int J Mol Sci Article Invasive urothelial carcinomas of the bladder (UCB) characteristically show a loss of differentiation markers. The transcription factor Grainyhead-like 3 (GRHL3) plays an important role in the development and differentiation of normal urothelium. The contribution to UCB progression is still elusive. Differential expression of GRHL3 was assessed in normal human urothelium and in non-invasive and invasive bladder cancer cell lines. The contribution of GRHL3 to cell proliferation, viability and invasion in UCB cell lines was determined by gain- and loss-of-function assays in vitro and in an organ culture model using de-epithelialized porcine bladders. GRHL3 expression was detectable in normal human urothelial cells and showed significantly higher mRNA and protein levels in well-differentiated, non-invasive RT4 urothelial carcinoma cells compared to moderately differentiated RT112 cells. GRHL3 expression was absent in anaplastic and invasive T24 cells. Ectopic de novo expression of GRHL3 in T24 cells significantly impaired their migration and invasion properties in vitro and in organ culture. Its downregulation improved the invasive capacity of RT4 cells. The results indicate that GRHL3 may play a role in progression and metastasis in UCB. In addition, this work demonstrates that de-epithelialized porcine bladder organ culture can be a useful, standardized tool to assess the invasive capacity of cancer cells. MDPI 2021-03-15 /pmc/articles/PMC8000182/ /pubmed/33803949 http://dx.doi.org/10.3390/ijms22062959 Text en © 2021 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
Wezel, Felix
Lustig, Johannes
Azoitei, Anca
Liu, Junnan
Meessen, Sabine
Najjar, Gregoire
Zehe, Viktor
Faustmann, Philipp
Zengerling, Friedemann
John, Axel
Martini, Thomas
Bolenz, Christian
Günes, Cagatay
Grainyhead-Like 3 Influences Migration and Invasion of Urothelial Carcinoma Cells
title Grainyhead-Like 3 Influences Migration and Invasion of Urothelial Carcinoma Cells
title_full Grainyhead-Like 3 Influences Migration and Invasion of Urothelial Carcinoma Cells
title_fullStr Grainyhead-Like 3 Influences Migration and Invasion of Urothelial Carcinoma Cells
title_full_unstemmed Grainyhead-Like 3 Influences Migration and Invasion of Urothelial Carcinoma Cells
title_short Grainyhead-Like 3 Influences Migration and Invasion of Urothelial Carcinoma Cells
title_sort grainyhead-like 3 influences migration and invasion of urothelial carcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000182/
https://www.ncbi.nlm.nih.gov/pubmed/33803949
http://dx.doi.org/10.3390/ijms22062959
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