Role of Stress Response Induced in Mesenchymal Stromal Cells in Extrinsic Drug Resistance of Human Tumor Cells
Project leader: Lucia Kučerová
Project duration: 2015 - 2018
Cells of the tumor microenvironment are recognized as major determinants of the tumor biology. The adjacent non-malignant cells regulate drug responses of the cancer cells by the secreted paracrine factors and interactions. Human mesenchymal stromal cells (MSC) actively contribute to many aspects of tumor biology including extrinsic effects on the drug responses in tumors. MSC were proven to exhibit increased drug resistance. The idea of the project is to examine the intracellular signaling pathways activated upon cytotoxic stimulus in human MSC because these were not described in detail. Moreover the stress response activated upon drug exposure may activate the cellular program preventing damage and promoting the tissue regeneration, and thus contribute to altered drug responses. We intend to evaluate the MSC-exerted effect on the drug responses in tumor cells, verify these effect on animal models and identify options for therapeutic augmentation based on the tumor microenvironment targeting.