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TGF-β isoforms induce EMT independent migration of ovarian cancer cells

BACKGROUND: Transforming growth factor beta (TGF-β) plays major roles in tumorigenesis by regulating cell growth, epithelial-to-mesenchymal transition (EMT), migration/invasion and metastasis. The epithelial markers E-cadherin, claudin-3 and claudin-4, commonly decreased in human adenocarcinomas are...

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Autores principales: Gao, Jingfang, Zhu, Yihong, Nilsson, Mikael, Sundfeldt, Karin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180856/
https://www.ncbi.nlm.nih.gov/pubmed/25278811
http://dx.doi.org/10.1186/s12935-014-0072-1
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author Gao, Jingfang
Zhu, Yihong
Nilsson, Mikael
Sundfeldt, Karin
author_facet Gao, Jingfang
Zhu, Yihong
Nilsson, Mikael
Sundfeldt, Karin
author_sort Gao, Jingfang
collection PubMed
description BACKGROUND: Transforming growth factor beta (TGF-β) plays major roles in tumorigenesis by regulating cell growth, epithelial-to-mesenchymal transition (EMT), migration/invasion and metastasis. The epithelial markers E-cadherin, claudin-3 and claudin-4, commonly decreased in human adenocarcinomas are actually up regulated during ovarian carcinogenesis. In human ovarian cancer TGF-β1 may either suppress or promote tumor progression, but whether other TGF-β isoforms (TGF-β2 and TGF-β3) exert similar effects is not known. METHODS: In this study we investigated the ability of the TGF-β isoforms (TGF-β1-3) to induce proliferation and migration by BrdU labeling, scratch wound and trans-filter migration assays in the human serous adenocarcinoma cell-line NIH-OVCAR3. Transepithelial resistance was measured and EMT observed by light-microscopy. Expression of adherens-, tight-junction and EMT-related transcription factors was analyzed by qRT-PCR and immunoblotting. RESULTS: All TGF-β isoforms dose-dependently inhibited NIH-OVCAR3 cell growth, stimulated tumor cell migration with similar efficiency. The mesenchymal marker N-cadherin and claudin-1 expression was induced and occludin down regulated. However, migrating cells retained an epithelial shape and E-cadherin expression. The E-cadherin repressor SNAIL mRNA levels remained low independently of TGF-β1-3 treatment while ZEB1 expression was enhanced. CONCLUSIONS: TGF-β1, TGF-β2 and TGF-β3 promote migration of NIH-OVCAR3 ovarian cancer cells independently of cell proliferation and without conversion to a complete EMT phenotype. Epithelial ovarian cancer commonly metastasis to the surrounding tissue or inside the peritoneum rather than invading blood vessels to set distance metastasis. Our result raises the question whether ovarian cancer primarily spread via collective migration than via single cell invasion.
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spelling pubmed-41808562014-10-03 TGF-β isoforms induce EMT independent migration of ovarian cancer cells Gao, Jingfang Zhu, Yihong Nilsson, Mikael Sundfeldt, Karin Cancer Cell Int Primary Research BACKGROUND: Transforming growth factor beta (TGF-β) plays major roles in tumorigenesis by regulating cell growth, epithelial-to-mesenchymal transition (EMT), migration/invasion and metastasis. The epithelial markers E-cadherin, claudin-3 and claudin-4, commonly decreased in human adenocarcinomas are actually up regulated during ovarian carcinogenesis. In human ovarian cancer TGF-β1 may either suppress or promote tumor progression, but whether other TGF-β isoforms (TGF-β2 and TGF-β3) exert similar effects is not known. METHODS: In this study we investigated the ability of the TGF-β isoforms (TGF-β1-3) to induce proliferation and migration by BrdU labeling, scratch wound and trans-filter migration assays in the human serous adenocarcinoma cell-line NIH-OVCAR3. Transepithelial resistance was measured and EMT observed by light-microscopy. Expression of adherens-, tight-junction and EMT-related transcription factors was analyzed by qRT-PCR and immunoblotting. RESULTS: All TGF-β isoforms dose-dependently inhibited NIH-OVCAR3 cell growth, stimulated tumor cell migration with similar efficiency. The mesenchymal marker N-cadherin and claudin-1 expression was induced and occludin down regulated. However, migrating cells retained an epithelial shape and E-cadherin expression. The E-cadherin repressor SNAIL mRNA levels remained low independently of TGF-β1-3 treatment while ZEB1 expression was enhanced. CONCLUSIONS: TGF-β1, TGF-β2 and TGF-β3 promote migration of NIH-OVCAR3 ovarian cancer cells independently of cell proliferation and without conversion to a complete EMT phenotype. Epithelial ovarian cancer commonly metastasis to the surrounding tissue or inside the peritoneum rather than invading blood vessels to set distance metastasis. Our result raises the question whether ovarian cancer primarily spread via collective migration than via single cell invasion. BioMed Central 2014-09-09 /pmc/articles/PMC4180856/ /pubmed/25278811 http://dx.doi.org/10.1186/s12935-014-0072-1 Text en © Gao et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Primary Research
Gao, Jingfang
Zhu, Yihong
Nilsson, Mikael
Sundfeldt, Karin
TGF-β isoforms induce EMT independent migration of ovarian cancer cells
title TGF-β isoforms induce EMT independent migration of ovarian cancer cells
title_full TGF-β isoforms induce EMT independent migration of ovarian cancer cells
title_fullStr TGF-β isoforms induce EMT independent migration of ovarian cancer cells
title_full_unstemmed TGF-β isoforms induce EMT independent migration of ovarian cancer cells
title_short TGF-β isoforms induce EMT independent migration of ovarian cancer cells
title_sort tgf-β isoforms induce emt independent migration of ovarian cancer cells
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180856/
https://www.ncbi.nlm.nih.gov/pubmed/25278811
http://dx.doi.org/10.1186/s12935-014-0072-1
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