Targeting extracellular vesicle-mediated tumor-stroma communication

• Applicant: Dr. Victoria Küttner
• Subject Area: Cell Biology ; Biochemistry ; Evolutionary Cell and Developmental Biology (Zoology)
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 261748796

Communication between cancer and stromal cells clearly plays a role in tumor progression. However, this knowledge has so far not been translated into effective therapies. This could be because tumor-stroma communication is still thought of as the exchange of individual signaling factors. However, over the last couple of years it has become clear that all cells release extracellular vesicles, which are membrane-encapsulated structures that carry multiple proteins from the donor to the recipient cells. It has been reported that bone marrow-derived cells promote metastasis upon uptake of extracellular vesicles from cancer cells. Using live-mouse microscopy, preliminary data show that tumor-growth-supporting fibroblasts release many-fold more extracellular vesicles than non-supportive fibroblasts. When a gene involved in extracellular vesicle release was suppressed, tumor-supportive fibroblasts were killed, whereas normal ones were not. I propose that extracellular vesicles are vehicles for tumor-stroma communication. Therefore, I aim to map the transfer of extracellular vesicles in tumors using a unique live-mouse imaging and a new, genetically encoded tagging method. Furthermore, I will use quantitative mass spectrometry-based proteomics to identify the proteins that are transferred by tumor-supportive fibroblasts to promote cancer cell growth. In a next step, I will specifically decrease expression levels of the identified proteins to test the effect on tumorigenicity in vivo. The results of this project will be a major contribution to the emerging field of extracellular vesicle-mediated communication in cancer and will set the stage for development of anti-cancer therapy through extracellular vesicle-targeting.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Mikala Egeblad, Ph.D.