A Novel Bioengineering Approach to Breast Cancer Invasion In Vitro Through Enhancing the Value of Existing Breast Cancer Epithelial Lineages

Abstract

Breast cancer incidence is rising globally. The emerging literature implicates cancer cell interactions with their surrounding microenvironment as a clinically significant driver of cell migration and metastasis. Current in vitro modelling approaches often rely on basic two-dimensional culture practices, a microenvironment far removed from the native tissue. This simplicity fails to recapitulate key aspects of the tumour environment that are critical to disease progression. This study has built upon three-dimensional culture technology to describe a breast cancer invasion assay with enhanced complexity compared with standard approaches. Three key breast epithelial cell lines, namely MCF-10A, MCF-7 and MDA-MB-231, representative of increasing invasiveness, were applied to in vitro systems of varying complexity. Through enhancing the geometry of the culture system, and inclusion of stromal populations, we have successfully improved breast cancer invasion modelling in vitro, exemplified by a demonstrated response to a test compound. The incorporation of a tissue-specific stromal foundation, upon which each epithelial cell lines were cultured, allowed for interaction between neosynthesised extracellular matrix and stromal and epithelial cells, whilst providing a dense physical network for cancer cells to migrate through. This has introduced several microenvironmental factors consistent with the native tissue but lacking in other more simplistic culture systems and has enhanced the value of commonplace cancer cell lines. This novel bioengineered culture system also lends itself to in-depth fundamental mechanistic insights into aspects of cancer cell biology, including interactions with the tissue environment and the role of cancer-associated fibroblasts in disease progression.