WP3

Objectives:

1. Integration of organ-resident microglia into established mini-brain model
2. Identify changes in microglia and matrix induced upon interaction with PCa cells in mini-brain OoC model
3. Test selected macrophage-targeted compounds to interfere with PCa cell survival and invasion into the mini-brain OoC

Expected Results: So-called mini-brain cultures of cerebral organoids differentiated from human stem cells develop into a complex organoid culture recapitulating the human brain. Co-cultures of these mini-brains with established tumour cell lines and patient-derived organoids of PCa mimic PCa invasion into brain. Early effects of metastasis on microglia function and matrix composition induced by invading PCa cells will be assessed. Selected druggable targets will be tested in the mini-brain system to validate their impact on PCa cell metastatic capacity.