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Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells
BACKGROUND: Recent epidemiological studies demonstrate that both active and involuntary exposure to tobacco smoke increase the risk of breast cancer. Little is known, however, about the molecular mechanisms by which continuous, long term exposure to tobacco smoke contributes to breast carcinogenesis...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750372/ https://www.ncbi.nlm.nih.gov/pubmed/23919753 http://dx.doi.org/10.1186/1476-4598-12-90 |
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author | Di Cello, Francescopaolo Flowers, V Lynn Li, Huili Vecchio-Pagán, Briana Gordon, Brent Harbom, Kirsten Shin, James Beaty, Robert Wang, Wei Brayton, Cory Baylin, Stephen B Zahnow, Cynthia A |
author_facet | Di Cello, Francescopaolo Flowers, V Lynn Li, Huili Vecchio-Pagán, Briana Gordon, Brent Harbom, Kirsten Shin, James Beaty, Robert Wang, Wei Brayton, Cory Baylin, Stephen B Zahnow, Cynthia A |
author_sort | Di Cello, Francescopaolo |
collection | PubMed |
description | BACKGROUND: Recent epidemiological studies demonstrate that both active and involuntary exposure to tobacco smoke increase the risk of breast cancer. Little is known, however, about the molecular mechanisms by which continuous, long term exposure to tobacco smoke contributes to breast carcinogenesis because most previous studies have focused on short term treatment models. In this work we have set out to investigate the progressive transforming effects of tobacco smoke on non-tumorigenic mammary epithelial cells and breast cancer cells using in vitro and in vivo models of chronic cigarette smoke exposure. RESULTS: We show that both non-tumorigenic (MCF 10A, MCF-12A) and tumorigenic (MCF7) breast epithelial cells exposed to cigarette smoke acquire mesenchymal properties such as fibroblastoid morphology, increased anchorage-independent growth, and increased motility and invasiveness. Moreover, transplantation experiments in mice demonstrate that treatment with cigarette smoke extract renders MCF 10A cells more capable to survive and colonize the mammary ducts and MCF7 cells more prone to metastasize from a subcutaneous injection site, independent of cigarette smoke effects on the host and stromal environment. The extent of transformation and the resulting phenotype thus appear to be associated with the differentiation state of the cells at the time of exposure. Analysis by flow cytometry showed that treatment with CSE leads to the emergence of a CD44(hi)/CD24(low) population in MCF 10A cells and of CD44(+) and CD49f (+) MCF7 cells, indicating that cigarette smoke causes the emergence of cell populations bearing markers of self-renewing stem-like cells. The phenotypical alterations induced by cigarette smoke are accompanied by numerous changes in gene expression that are associated with epithelial to mesenchymal transition and tumorigenesis. CONCLUSIONS: Our results indicate that exposure to cigarette smoke leads to a more aggressive and transformed phenotype in human mammary epithelial cells and that the differentiation state of the cell at the time of exposure may be an important determinant in the phenotype of the final transformed state. |
format | Online Article Text |
id | pubmed-3750372 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-37503722013-08-24 Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells Di Cello, Francescopaolo Flowers, V Lynn Li, Huili Vecchio-Pagán, Briana Gordon, Brent Harbom, Kirsten Shin, James Beaty, Robert Wang, Wei Brayton, Cory Baylin, Stephen B Zahnow, Cynthia A Mol Cancer Research BACKGROUND: Recent epidemiological studies demonstrate that both active and involuntary exposure to tobacco smoke increase the risk of breast cancer. Little is known, however, about the molecular mechanisms by which continuous, long term exposure to tobacco smoke contributes to breast carcinogenesis because most previous studies have focused on short term treatment models. In this work we have set out to investigate the progressive transforming effects of tobacco smoke on non-tumorigenic mammary epithelial cells and breast cancer cells using in vitro and in vivo models of chronic cigarette smoke exposure. RESULTS: We show that both non-tumorigenic (MCF 10A, MCF-12A) and tumorigenic (MCF7) breast epithelial cells exposed to cigarette smoke acquire mesenchymal properties such as fibroblastoid morphology, increased anchorage-independent growth, and increased motility and invasiveness. Moreover, transplantation experiments in mice demonstrate that treatment with cigarette smoke extract renders MCF 10A cells more capable to survive and colonize the mammary ducts and MCF7 cells more prone to metastasize from a subcutaneous injection site, independent of cigarette smoke effects on the host and stromal environment. The extent of transformation and the resulting phenotype thus appear to be associated with the differentiation state of the cells at the time of exposure. Analysis by flow cytometry showed that treatment with CSE leads to the emergence of a CD44(hi)/CD24(low) population in MCF 10A cells and of CD44(+) and CD49f (+) MCF7 cells, indicating that cigarette smoke causes the emergence of cell populations bearing markers of self-renewing stem-like cells. The phenotypical alterations induced by cigarette smoke are accompanied by numerous changes in gene expression that are associated with epithelial to mesenchymal transition and tumorigenesis. CONCLUSIONS: Our results indicate that exposure to cigarette smoke leads to a more aggressive and transformed phenotype in human mammary epithelial cells and that the differentiation state of the cell at the time of exposure may be an important determinant in the phenotype of the final transformed state. BioMed Central 2013-08-06 /pmc/articles/PMC3750372/ /pubmed/23919753 http://dx.doi.org/10.1186/1476-4598-12-90 Text en Copyright © 2013 Di Cello et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Di Cello, Francescopaolo Flowers, V Lynn Li, Huili Vecchio-Pagán, Briana Gordon, Brent Harbom, Kirsten Shin, James Beaty, Robert Wang, Wei Brayton, Cory Baylin, Stephen B Zahnow, Cynthia A Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells |
title | Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells |
title_full | Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells |
title_fullStr | Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells |
title_full_unstemmed | Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells |
title_short | Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells |
title_sort | cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750372/ https://www.ncbi.nlm.nih.gov/pubmed/23919753 http://dx.doi.org/10.1186/1476-4598-12-90 |
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