Tissue Eng Part A. 2018 Mar 8. doi: 10.1089/ten.TEA.2017.0509. [Epub ahead of print]

An engineered human adipose/collagen model for in vitro breast cancer cell migration studies.

Hume RD¹, Berry L², Reichelt S³, D'Angelo M⁴, Gomm J⁵, Cameron RE⁶, Watson C⁷.

Abstract

Adipocytes are one of the major stromal cell components of the human breast. These cells play a key role in the development of the gland and are implicated in breast tumorigenesis. Frequently, directional stromal collagen I fibres are found surrounding aggressive breast tumours. These fibres enhance breast cancer cell migration and are associated with poor patient prognosis. We sought to recapitulate these stromal components in vitro to provide a 3D model comprising human adipose tissue and anisotropic collagen fibres. We developed a human mesenchymal stem cell (hMSC) cell line capable of undergoing differentiation into mature adipocytes by immortalising hMSCs, isolated from breast reduction mammoplasties, via retroviral transduction. These immortalised hMSCs were seeded in engineered collagen I scaffolds with directional internal architecture and adipogenesis was chemically induced, resulting in human adipose tissue being synthesised in vitro in an architectural structure associated with breast tumorigenesis. Subsequently, fluorescently labelled from an established breast cancer cell line were seeded into this model, co-cultured for 7 days and imaged using multiphoton microscopy. Enhanced breast cancer cell migration was observed in the adipose-containing model over empty scaffold controls, demonstrating an adipocyte-mediated influence on breast cancer cell migration. Thus, this 3D in vitro model recapitulates the migratory effects of adipocytes observed on breast cancer cells and suggests that it could have utility with fresh breast tumour biopsies as an assay for cancer therapeutic efficacy in personalised medicine strategies.