Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells
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  • 作者:Francescopaolo Di Cello (5)
    V Lynn Flowers (5)
    Huili Li (5)
    Briana Vecchio-Pagán (5)
    Brent Gordon (5)
    Kirsten Harbom (5)
    James Shin (5)
    Robert Beaty (5)
    Wei Wang (5)
    Cory Brayton (6)
    Stephen B Baylin (5)
    Cynthia A Zahnow (5)
  • 关键词:Tobacco ; Breast cancer ; Cell motility and invasion ; Epithelial to mesenchymal transition ; Metastasis ; Intraductal injection
  • 刊名:Molecular Cancer
  • 出版年:2013
  • 出版时间:December 2013
  • 年:2013
  • 卷:12
  • 期:1
  • 全文大小:1175KB
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  • 作者单位:Francescopaolo Di Cello (5)
    V Lynn Flowers (5)
    Huili Li (5)
    Briana Vecchio-Pagán (5)
    Brent Gordon (5)
    Kirsten Harbom (5)
    James Shin (5)
    Robert Beaty (5)
    Wei Wang (5)
    Cory Brayton (6)
    Stephen B Baylin (5)
    Cynthia A Zahnow (5)

    5. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 21287, USA
    6. Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
  • ISSN:1476-4598
文摘
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 CD44hi/CD24low 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.

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