Identification of macrophage function and matrix composition changes induced by the first interaction with invading prostate and breast cancer cells in the liver organ-on-chip model

Objectives:

  1. Establish standardized human liver OoC integrated with (age-relevant) organ-resident and blood monocyte-derived macrophage population;
  2. Identify macrophage and matrix changes induced upon interaction with PCa/BCa cells in liver OoC model;
  3. Select and test potential macrophage-targeted compounds to interfere PCa cell survival and invasion.

Expected Results: Liver microtissues of primary human hepatocytes, liver endothelial cells and (age-relevant) Kupffer cells are embedded in age-appropriate liver matrix and co-cultured with various PCa and BCa cells to faithfully mimic the early steps of invasion into liver. This optimised and controlled (MIVO) OoC system will deliver the very early biomarkers of macrophage changes induced by cancer cell interaction and impacting macrophage function and matrix composition. Selected druggable targets will be tested in the OoC to validate their impact on PCa cell survival and invasion.

Selection and interviews ongoing