Tine Thurison Sørensen

Research assistant

Key Research Interests
Production of monoclonal antibodies, design of quantitative immunoassays, uPAR cleavage and cancer invasion.

Current projects
Cancer invasion requires tissue remodeling including breakdown of the extracellular matrix. The main enzyme systems involved in these processes are the matrix metalloproteinases and the plasminogen activation system. The key components of the plasminogen activation system are the serine protease urokinase plasminogen activator (uPA) and its cellular receptor uPAR. Binding to uPAR localizes uPA to the cell surface, where uPA activates plasminogen to plasmin. In most cancers, uPA and uPAR are localized at the invasive front of the tumor. Several studies have shown that uPAR, uPA, and its physiological inhibitor PAI-1 are prognostic markers, when measured in clinical samples from cancer patients. Intact uPAR, consisting of three domains [uPAR(I-III)] connected by two linker regions, is anchored to the plasma membrane by a glycolipid anchor (GPI) on domain III. uPAR can be cleaved in the linker region between domain I and II, liberating uPAR domain I (uPAR(I)), while the cleaved uPAR(II-III) remains bound to the cell surface. Several proteases can cleave uPAR in vitro, whereas only uPA have been demonstrated to cleave in vivo.

The aim of my current project is to advance our knowledge on the uPAR cleavage and its involvement in cancer invasion and metastasis. To accomplish this, I will identify and quantify cleaved muPAR forms in tumor tissue and blood from cancer mouse models. Using a transplanted syngenic model and a transgene mouse model which spontaneously develops breast tumors, I will study uPAR cleavage and the levels of the uPAR forms in blood and tumor tissue to elucidate the putative physiological significance of uPAR cleavage during cancer progression. An understanding of the uPAR cleavage, its mechanism and the potential functions of the cleaved forms is necessary to clarify the impact of the uPAR cleavage on processes related to cancer progression and to elucidate if the cleavage and/or the cleaved uPAR forms could be targets for anticancer therapy.

Career
2009-present: Research Assistant, The Finsen Laboratory.

2007-2009: Master project at The Finsen Laboratory: Design and validation of Time-Resolved Fluorescence immunoassay for detection of uPAR(I) in patient material.

2004-2009: M. Sc. Molecular Biomedicine, University of Copenhagen