Organotypic platform for studying cancer cell metastasis

Metastasis is the leading cause of mortality in cancer patients. To migrate to distant sites, cancer cells would need to adapt their behaviour in response to different tissue environments. Thus, it is essential to study this process in models that can closely replicate the tumour microenvironment. Here, we evaluate the use of organotypic liver and brain slices to study cancer metastasis. Morphological and viability parameters of the slices were monitored daily over 3 days in culture to assess their stability as a realistic 3D tissue platform for in vitro metastatic assays. Using these slices, we evaluated the invasion of MDA-MB-231 breast cancer cells and of a subpopulation that was selected for increased motility. We show that the more aggressive invasion of the selected cells likely resulted not only from their lower stiffness, but also from their lower adhesion to the surrounding tissue. Different invasion patterns in the brain and liver slices were observed for both subpopulations. Cells migrated faster in the brain slices (with an amoeboid-like mode) compared to in the liver slices (where they migrated with mesenchymal or collective migration-like modes). Inhibition of the Ras/MAPK/ERK pathway increased cell stiffness and adhesion forces, which resulted in reduced invasiveness. These results illustrate the potential for organotypic tissue slices to more closely mimic in vivo conditions during cancer cell metastasis than most in vitro models.

Automated summary

Metastasis is the primary cause of cancer patient mortality, and studying this process using organotypic liver and brain slices shows promise in closely replicating the tumour microenvironment for in vitro testing. Different invasion patterns and behaviors were observed in the breast cancer cells within the brain and liver slices, with variations in cell stiffness and adhesion forces influencing invasiveness. Inhibition of the Ras/MAPK/ERK pathway resulted in reduced invasiveness, highlighting the potential of organotypic tissue slices to better mimic in vivo conditions during cancer cell metastasis compared to traditional in vitro models.