The role of syntenin in the establishment of a favorable tumor microenvironment in human breast cancer

• Applicant: Dr. Kerstin Menck
• Subject Area: Cell Biology ; Hematology, Oncology
• Term: from 2015 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 277046854

Breast cancer is the most common cancer in women worldwide and accounts for 28% of the total cancer cases in the European Region of the World Health Organisation (WHO). Breast cancers compose complex tissues whereby tumor cells are surrounded by a variety of benign stroma cells (e.g. cells of the connective tissue, immune cells or blood vessel cells). The tumor cells are able to influence these stroma cells, thereby creating a favorable tumor niche which promotes tumor progression. Recent studies show that these tumor-stroma interactions are largely mediated by extracellular vesicles. These are small vesicles (diameter <1µm) which are released from inside the cell or from the cell surface and are able to transport molecules to surrounding cells. However, specific factors which regulate vesicle-mediated tumor-stroma communication and might represent promising novel targets for therapy are still unknown. Analyses of patient samples revealed that the protein syntenin is overexpressed in advanced human breast cancer, its expression level inversely correlating with patient survival. Interestingly, syntenin controls the biogenesis of extracellular vesicles and the export of various tumor-supporting proteins to these vesicles. However, the significance of syntenin-positive vesicles for tumor-stroma interactions has not been investigated so far. The present project will address this question by first using a proteomics approach to identify which tumor-supporting proteins are exported to tumor vesicles by syntenin. Subsequently, the significance of syntenin-positive vesicles for tumor-stroma interactions will be assessed in vitro and in a syngeneic mouse model of breast cancer. Novel syntenin inhibitors will be tested for their efficiency to antagonize the pro-tumoral tumor-stroma crosstalk.

• DFG Programme: Research Fellowships
• International Connection: France
• Host: Professorin Dr. Pascale Zimmermann