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

Claire E. Nash, Georgia Mavria, Euan W. Baxter, Deborah L. Holliday, Darren C. Tomlinson, Darren Treanor, Vera Novitskaya, Fedor Berditchevski, Andrew M. Hanby, Valerie Speirs*

*Corresponding author for this work

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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.

Original languageEnglish
Pages (from-to)13731-13741
Number of pages11
JournalOncotarget
Volume6
Issue number15
Early online date12 Apr 2015
DOIs
Publication statusPublished - 2015

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Keywords

  • 3D cell culture
  • Breast
  • HER2

ASJC Scopus subject areas

  • Oncology

Cite this

Nash, C. E., Mavria, G., Baxter, E. W., Holliday, D. L., Tomlinson, D. C., Treanor, D., Novitskaya, V., Berditchevski, F., Hanby, A. M., & Speirs, V. (2015). Development and characterisation of a 3D multi-cellular in vitro model of normal human breast: A tool for cancer initiation studies. Oncotarget, 6(15), 13731-13741. https://doi.org/10.18632/oncotarget.3803