The Effect of Cancer Associated Fibroblasts and Matrix Stiffness on Invasion of HNSCC in TRACER

Dean, Teresa 1 ;  McGuigan, Alison 1, 2

1. Institute of Biomaterials and Bioengineering, University of Toronto; 2. Department of Chemical Engineering and Applied Chemistry

Head and neck cancer (HNSCC) has a high propensity for local invasion and metastasis, and prognosis is poor once metastasis has occurred. Currently, successful treatments to prevent invasion and metastasis in HNSCC do not exist. The assessment of drug effectiveness in cancer often takes place on two-dimensional cell culture platforms, due to ease of analysis and cost efficiency. However, 2D cultures do not recapitulate the heterogenous tumor microenvironment or three dimensional architecture of tumors, both of which have been demonstrated to have an effect on tumor cell behaviour and phenotype.

In order to recapitulate these characteristics in a simple in vitro model, our lab has developed a novel three dimensional cell culture platform, Tissue Roll for Analysis of Cellular Response (TRACER). In TRACER, cells are mixed with a collagen gel (the major extracellular matrix component of tumours) and seeded into a porous paper scaffold. These biocomposites are then wrapped around an aluminum mandrel in order to recapitulate the 3D architecture of in vivo tumours. In TRACER, tumor heterogeneity may by recapitulated through the incorporation of multiple cell types; additionally, cells may be patterned such that tissue architecture of either early or advanced disease is recreated. Importantly, TRACER end-point analysis is easier than in other models which recapitulate aspects of the tumour microenvironment.

We are specifically interested in investigating the role that a stromal cell type, cancer associated fibroblasts (CAFs) plays in the promotion of invasiveness and proliferation in HNSCC cells in TRACER, as CAFs have previously been demonstrated to promote the proliferation and invasion of tumour cells.

Additionally, tumour stiffness has been implicated in a more invasive tumour cell phenotype. By varying the concentration of collagen in our tumour model, we will investigate the ability of an increasing extracellular matrix stiffness in tandem with the presence of CAFs to promote an invasive phenotype in HNSCC tumour cells.