Development and characterisation of a 3D multi-cellular in vitro model of normal human breast: a tool for cancer initiation studies

Research output: Contribution to journalArticlepeer-review

Authors

  • Claire Nash
  • Georgia Mavria
  • Euan Baxter
  • Deborah Holliday
  • Darren C Tomlinson
  • Darren Treanor
  • Andrew Hanby
  • Valerie Speirs

Colleges, School and Institutes

External organisations

  • University of Leeds

Abstract

Multicellular 3-dimensional (3D) in vitro models of normal human breast tissue to study cancer initiation are required. We present a model incorporating three of the major functional cell types of breast, detail the phenotype and document our breast cancer initiation studies. Myoepithelial cells and fibroblasts were isolated and immortalised from breast reduction mammoplasty samples. Tri-cultures containing non-tumorigenic luminal epithelial cells HB2, or HB2 overexpressing different HER proteins, together with myoepithelial cells and fibroblasts were established in collagen I. Phenotype was assessed morphologically and immunohistochemically and compared to normal breast tissue. When all three cell types were present, polarised epithelial structures with lumens and basement membrane production were observed, akin to normal human breast tissue. Overexpression of HER2 or HER2/3 caused a significant increase in size, while HER2 overexpression resulted in development of a DCIS-like phenotype. In summary, we have developed a 3D tri-cellular model of normal human breast, amenable to comparative analysis after genetic manipulation and with potential to dissect the mechanisms behind the early stages of breast cancer initiation.

Details

Original languageEnglish
Pages (from-to)13731-13741
Number of pages11
JournalOncoTarget
Volume6
Issue number15
Publication statusPublished - 30 May 2015

Keywords

  • Breast, Breast Neoplasms, Cell Culture Techniques, Female, Humans, Imaging, Three-Dimensional, Immunohistochemistry, Radioimmunodetection, Receptor, ErbB-2, Receptor, ErbB-3, Journal Article, Research Support, Non-U.S. Gov't

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