Stromal cell expression of caveolin-1 predicts outcome in breast cancer

Am J Pathol. 2009 Jun;174(6):2035-43. doi: 10.2353/ajpath.2009.080924. Epub 2009 May 1.

Abstract

Caveolin-1 has been linked to tumor progression and clinical outcome in breast cancer, but a clear resolution of its role as a prognostic marker is lacking. We assessed caveolin-1 levels in normal breast tissue and two breast cancer cohorts for which outcome data were available. We found that caveolin-1 was not expressed in normal breast luminal epithelium but was present in the epithelial compartment of some tumors. We found no association between caveolin-1 expression in the epithelial compartment and clinical outcome. However, high levels of caveolin-1 in the stromal tissue surrounding the tumor, rather than within tumor cells, associated strongly with reduced metastasis and improved survival (P < 0.0001). The onset of mammary tumors driven by Her2/neu overexpression was accelerated in mice lacking caveolin-1, thereby supporting the observation that the presence of caveolin-1 in the tumor microenvironment modulates tumor development. These studies suggest that stromal caveolin-1 expression may be a potential therapeutic target and a valuable prognostic indicator of breast cancer progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Caveolin 1 / biosynthesis*
  • Caveolin 1 / genetics
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / biosynthesis
  • Receptors, Progesterone / biosynthesis
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism
  • Stromal Cells / metabolism*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Caveolin 1
  • Fam89b protein, mouse
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptors, Virus
  • Receptor, ErbB-2