Human mammospheres secrete hormone-regulated active extracellular vesicles

PLoS One. 2014 Jan 3;9(1):e83955. doi: 10.1371/journal.pone.0083955. eCollection 2014.

Abstract

Breast cancer is a leading cause of cancer-associated death worldwide. One of the most important prognostic factors for survival is the early detection of the disease. Recent studies indicate that extracellular vesicles may provide diagnostic information for cancer management. We demonstrate the secretion of extracellular vesicles by primary breast epithelial cells enriched for stem/progenitor cells cultured as mammospheres, in non-adherent conditions. Using a proteomic approach we identified proteins contained in these vesicles whose expression is affected by hormonal changes in the cellular environment. In addition, we showed that these vesicles are capable of promoting changes in expression levels of genes involved in epithelial-mesenchymal transition and stem cell markers. Our findings suggest that secreted extracellular vesicles could represent potential diagnostic and/or prognostic markers for breast cancer and support a role for extracellular vesicles in cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell-Derived Microparticles / metabolism*
  • Computational Biology
  • Epithelial-Mesenchymal Transition
  • Extracellular Space / metabolism*
  • Female
  • Gene Expression
  • Hormones / metabolism*
  • Humans
  • Mammary Glands, Human / metabolism*
  • Neoplastic Stem Cells / metabolism
  • Primary Cell Culture
  • Protein Interaction Maps
  • Proteome
  • Proteomics / methods
  • Reproducibility of Results
  • Spheroids, Cellular
  • Tamoxifen / pharmacology

Substances

  • Hormones
  • Proteome
  • Tamoxifen

Grants and funding

This work was supported by grants from: Foundation La Caixa (MP), Foundation for Science and Technology of the Portuguese Ministry of Science (BS), the Institute of Health Carlos III (06/0621 & 09/00526 to JMFP and PI081877 to MdMV), the program Ramon y Cajal (JMFP), the Departments of Education and Health of the Government of the Autonomous Community of the Basque Country (MdMV) and the Department of Industry, Tourism and Trade (Etortek). Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd) is funded by the Institute of Health Carlos III. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.