Spatial transcriptome profiling ofin vitro3D tumouroids to study tumour-stroma interactions

Abstract

Bioengineering facets of the tumour microenvironment (TME) are essential in 3D tissue models to accurately recapitulate tumour progression. Stromal cells are key components of the TME and their incorporation into 3D biomimetic bioengineered tumour-stroma models is essential to be able to mimic the TME. By engineering tumouroids with distinct tumour and stromal compartments, it has been possible to identify how gene expression is altered by the presence of different stromal cells using spatial transcriptomics. Ameloblastoma is a benign epithelial tumour of the jawbone and in engineered multi-compartment tumouroids increased expression of oncogenes was found where osteoblasts (bone stroma) were present. Engineering a gingival fibroblast stroma resulted in increased matrix remodelling genes in the ameloblastoma tumour. This study provides evidence to show the stromal specific effect on tumour behaviour and illustrates the importance of engineering biologically relevant stroma for engineered tumour models. Our novel results show that an engineered fibroblast stroma causes the upregulation of matrix remodelling genes in ameloblastoma which directly correlates to measured invasion in the model. In contrast the presence of an osteoblast/bone stroma increases the expression of oncogenes by ameloblastoma cells.