Work Package 2: European Prostate Cancer Model Platform (EPCM)
As in the breast and lung Work Packages, the prostate cancer (PrCa) Work Package strives to create and compare – side by side - novel, reproducible and robust in vitro platforms for target validation. These complex platforms specifically aim to mimic the dynamics, complexity and heterogeneity of tumours in situ.
For this purpose, WP2 compiles materials from patients, cell lines, innovative xenograft models, and primary tissues & cells from genetically engineered mouse models (GEMMs) (PTEN-KO). Based on this spectrum of materials, tissue slices, simple 2D, 3D, and complex organotypic co-culture models of tumour cells with stromal fibroblasts are generated. Paraffin embedded materials from the individual platforms will be arrayed on tissue-micro arrays (TMAs) and analysed and compared to each other as well as original patient tumors for protein expression characterising proliferation, survival and cell death, stress-pathway activation and patterns of androgen-dependent expression.
A particular focus within WP2 (in close collaboration with WP4) is on real-time, live cell imaging and the dynamic evaluation of tissue heterogeneity. The goal is to use advanced imaging subsequently for both 3D models and tissue slices.
The fidelity with which the various model platforms represent human prostate tumours will be studied using strictly controlled conditions. For this purpose, a small set of carefully selected drugs such as anti-androgens will be used and the activity of key cell signalling pathways active in resting versus perturbed conditions will be systematically addressed.
The data generated will then be compared with clinical pathology & histology, again using standardized clinical microscopy, automated image analysis and statistical evaluation tools.