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PyMT-1099, a versatile murine cell model for EMT in breast cancer

An epithelial-mesenchymal transition (EMT) has been implicated in cancer metastasis, drug resistance, and in conferring stem cell-like traits to cancer cells. Most studies investigating EMT in cancer have either utilized immortalized or cancer cell lines that are already primed to undergo an EMT and...

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Autores principales: Saxena, Meera, Kalathur, Ravi Kiran Reddy, Neutzner, Melanie, Christofori, Gerhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092323/
https://www.ncbi.nlm.nih.gov/pubmed/30108334
http://dx.doi.org/10.1038/s41598-018-30640-1
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author Saxena, Meera
Kalathur, Ravi Kiran Reddy
Neutzner, Melanie
Christofori, Gerhard
author_facet Saxena, Meera
Kalathur, Ravi Kiran Reddy
Neutzner, Melanie
Christofori, Gerhard
author_sort Saxena, Meera
collection PubMed
description An epithelial-mesenchymal transition (EMT) has been implicated in cancer metastasis, drug resistance, and in conferring stem cell-like traits to cancer cells. Most studies investigating EMT in cancer have either utilized immortalized or cancer cell lines that are already primed to undergo an EMT and do not adequately represent a fully differentiated epithelial state in the absence of an EMT induction. Hence, model systems are required which recapitulate all stages of EMT in cancer cells. Here, we report the derivation and characterization of epithelial PyMT-1099 cancer cells from the MMTV-PyMT mouse model of breast cancer. We demonstrate that PyMT-1099 cells undergo an EMT upon TGFβ treatment, while upon TGFβ withdrawal they go through a mesenchymal-epithelial transition (MET), as assessed by changes in cell morphology and marker expression and comparable to normal murine mammary gland NMuMG cells. However, in contrast to NMuMG cells, PyMT-1099 cells show an increase in cell migration and are highly tumorigenic and metastatic when transplanted into immunocompromised mice. Finally, we report cancer cell-specific changes in gene expression during EMT of PyMT-1099 cells not found in non-transformed NMuMG cells. Thus, PyMT-1099 cells are a versatile tool to study breast cancer-associated EMT and MET in vitro and in vivo.
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spelling pubmed-60923232018-08-20 PyMT-1099, a versatile murine cell model for EMT in breast cancer Saxena, Meera Kalathur, Ravi Kiran Reddy Neutzner, Melanie Christofori, Gerhard Sci Rep Article An epithelial-mesenchymal transition (EMT) has been implicated in cancer metastasis, drug resistance, and in conferring stem cell-like traits to cancer cells. Most studies investigating EMT in cancer have either utilized immortalized or cancer cell lines that are already primed to undergo an EMT and do not adequately represent a fully differentiated epithelial state in the absence of an EMT induction. Hence, model systems are required which recapitulate all stages of EMT in cancer cells. Here, we report the derivation and characterization of epithelial PyMT-1099 cancer cells from the MMTV-PyMT mouse model of breast cancer. We demonstrate that PyMT-1099 cells undergo an EMT upon TGFβ treatment, while upon TGFβ withdrawal they go through a mesenchymal-epithelial transition (MET), as assessed by changes in cell morphology and marker expression and comparable to normal murine mammary gland NMuMG cells. However, in contrast to NMuMG cells, PyMT-1099 cells show an increase in cell migration and are highly tumorigenic and metastatic when transplanted into immunocompromised mice. Finally, we report cancer cell-specific changes in gene expression during EMT of PyMT-1099 cells not found in non-transformed NMuMG cells. Thus, PyMT-1099 cells are a versatile tool to study breast cancer-associated EMT and MET in vitro and in vivo. Nature Publishing Group UK 2018-08-14 /pmc/articles/PMC6092323/ /pubmed/30108334 http://dx.doi.org/10.1038/s41598-018-30640-1 Text en © The Author(s) 2018 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Saxena, Meera
Kalathur, Ravi Kiran Reddy
Neutzner, Melanie
Christofori, Gerhard
PyMT-1099, a versatile murine cell model for EMT in breast cancer
title PyMT-1099, a versatile murine cell model for EMT in breast cancer
title_full PyMT-1099, a versatile murine cell model for EMT in breast cancer
title_fullStr PyMT-1099, a versatile murine cell model for EMT in breast cancer
title_full_unstemmed PyMT-1099, a versatile murine cell model for EMT in breast cancer
title_short PyMT-1099, a versatile murine cell model for EMT in breast cancer
title_sort pymt-1099, a versatile murine cell model for emt in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092323/
https://www.ncbi.nlm.nih.gov/pubmed/30108334
http://dx.doi.org/10.1038/s41598-018-30640-1
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