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Volume 12 Supplement 1

Breast Cancer Research 2010

Modelling breast cancer in a three-dimensional heterotypic culture system

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Microenvironmental factors are fundamental in the regulation of normal and tumour breast tissue. Two cell types have been implicated in having opposing effects on breast tumour cell behaviour: myoepithelial cells exhibit broad tumour-suppressor activity, whilst fibroblasts frequently promote tumour growth and invasion. Previous work has described the development of a physiologically relevant three-dimensional heterotypic culture system containing tumour, myoepithelial and fibroblast cells. The data showed organisation of the cells into co-unit structures recapitulating ductal carcinoma in situ breast, with homing of myoepithelial cells around luminal cells, and highlighted a central role for tumour-associated fibroblasts in disrupting ductal carcinoma in situ structures. This study describes further manipulation of the model to include tumour cells that represent the heterogeneity of breast cancer.

MCF-7 (ER+), MDA-MB-468, MDA-MB-231 (basal) and MDA-MB-453 (Her2+) were cultured in collagen for 7 days in the presence or absence of normal myoepithelial cells. Gels were fixed in formalin, paraffin embedded and immunohistochemistry was performed for a series of markers recognising the cell types along with basal polarity and basement membrane proteins.

Initial morphological analysis of the cultures has been performed to assess the degree of co-unit formation, based on a visual description of the size and shape of the co-units. Co-unit formation has been employed as a representative measure of tumour progression as it is known to be a key feature in early breast cancer invasion. When cultured alone, MCF-7 and MDA-MB-468 cells formed spherical co-unit structures and this was maintained in the presence of myoepithelial cells. In contrast, MDA-MB-231 and MDA-MB-453 cells show a more scattered appearance. The presence of myoepithelial cells induced polarity in the MDA-MB-231 cells and a more ordered appearance.

This study is the first time that the co-culture of tumour cell populations with myoepithelial cells has been investigated in three-dimensional collagen gels showing differences in morphology that may relate to tumour progression.

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Correspondence to DL Holliday.

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Keywords

  • Breast Cancer
  • Myoepithelial Cell
  • Breast Tumour Cell
  • Promote Tumour Growth
  • Luminal Cell