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Authors Koch, K.M. ; Jaeschke, A. ; Murekatete, B. ; Ravichandran, A. ; Tsurkan, M. ; Werner, C. ; Soon, P. ; Hutmacher, D. W. ; Haupt, L.M. ; Bray, L.
Title Stromal fibroblasts regulate microvascular-like network architecture in a bioengineered breast tumour angiogenesis model
Date 24.09.2020
Number 58866
Abstract The plasticity of the tumour microenvironment is a key contributor to cancer development and progression. Here, we present a bioengineered breast tumour angiogenesis model comprised of mammary derived epithelial, endothelial and fibroblast cells, to dissect the mechanisms of cancer-associated fibroblasts (CAFs) on microvascular-like network formation and epithelial spheroid morphology. Primary patient-derived mammary endothelial cells, normal breast fibroblasts (NBF, patient matched) and CAFs were cultured within three-dimensional (3D) semi-synthetic hydrogels where CAFs promoted an increase in the density and morphology of the microvascular-like network. The mammary microenvironment also increased the number of MCF-10a epithelial spheroids when compared with a non-mammary microenvironment, and a malignant mammary microenvironment resulted in further morphological differences in the epithelial spheroids. The morphological changes observed following interactions between breast CAFs and endothelial cells, highlight the plasticity of the malignant stroma in tumour vascularisation. Our in vitro bioengineered breast cancer microenvironment provides a robust model to study cell-cell and cell-matrix interactions.
Publisher Acta Biomaterialia
Identifier
Citation Acta Biomaterialia 114 (2020) 256-269
DOI https://doi.org/10.1016/J.ACTBIO.2020.07.036
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