DEVELOPMENT AND CHARACTERIZATION OF T-SLICE: A CANCER MODELING PLATFORM TO MODEL IMPORTANT FEATURES OF THE TUMOUR MICROENVIRONMENT IN VITRO

Abstract

The tumour microenvironment is composed of several types of non-cancerous cells (e.g., cancer-associated fibroblasts, endothelial cells, immune cells), extracellular matrix proteins, and cell signaling molecules. The various components of the tumour microenvironment work together to generate biochemical and biophysical pressures that promote tumour growth, invasion, metastasis, and multidrug resistance. Hypoxia gradients in the tumour microenvironment are significant because they are responsible for driving many of the tumour cell responses that allow the cancer to progress. The current landscape of in vitro cancer modeling relies largely on methods that fail to incorporate important features of the tumour microenvironment. As a result, investigations into tumour biology and anti-cancer drug efficacy can be misrepresentative of what occurs in the natural tumour in vivo. Cancer modeling platforms that do mimic important features of the tumour microenvironment are often limited due to their incompatibility with live-imaging techniques, lack of tunability, and lack of usability due to cost or the need for user expertise. The aim of this research project was to create a cancer disease modeling device that can recapitulate important features of the tumour microenvironment while remaining imageable to acquire spatiotemporal information. We have combined 2D tissue culture with 3D spheroid culture to create the “Tumour Spheroids Layered in an Imageable Cancer Environment” (T-SLICE), which harnesses the advantages of currently established cancer research methods while circumventing their limitations. This study demonstrated that T-SLICE generates hypoxia gradients that impact tumour cell response in two different breast cancer cell lines, including viability, proliferation rate, and changes in gene expression. T-SLICE provides a live snapshot of cancer cell behaviour in response to different biochemical pressures and has the potential to advance anti-cancer drug testing and diagnosis in the future.