In Vivo Effects of Long-Term Cigarette Smoke Exposure on Mammary Tissue in Mice

Am J Pathol. 2017 Jun;187(6):1238-1244. doi: 10.1016/j.ajpath.2017.02.004. Epub 2017 Apr 4.

Abstract

Cigarette smoking is the leading cause of preventable death worldwide and has been linked to the development and progression of cancer. Many cohort studies have described the link between patients with breast cancer and those with long-term smoking history. Despite the claim of correlation, the mechanism by which cigarette smoke alters normal breast epithelial cells and stroma and contributes to tumor cell growth remains undefined. To investigate whether cigarette smoke promotes ductal epithelial cell hyperplasia by stimulating stromal endothelial cell proliferation, we exposed mice to cigarette smoke for 6 months. We observed epithelial proliferation, increased fibrosis, increased vascularity, and mast cell infiltration. This is the first study to look at the in vivo changes in the breast after long-term cigarette smoke exposure and provides a novel insight to understanding how cigarette smoke contributes to early changes that may contribute to tumor formation and progression. In conclusion, this study suggests that cigarette smoke modulates key stromal-epithelial interactions to support increased angiogenesis, desmoplasia, and abnormal ductal epithelial cell growth.

MeSH terms

  • Animals
  • Cell Proliferation
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Collagen / metabolism
  • Epithelial Cells / pathology
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Fibrosis / pathology
  • Hyperplasia / etiology
  • Hyperplasia / pathology
  • Inflammation / etiology
  • Inflammation / pathology
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Animal / pathology*
  • Mammary Neoplasms, Experimental / etiology*
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mast Cells / pathology
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic
  • Smoking / adverse effects
  • Smoking / pathology*
  • Stromal Cells / pathology

Substances

  • Extracellular Matrix Proteins
  • Collagen