Biologisk funktion för mastcellstryptas: cancer och andra aspekter
Tidsperiod: 2021-01-01 till 2023-12-31
Projektledare: Gunnar Pejler
Budget: 2 400 000 SEK
Mast cells are currently emerging as major players in a variety of pathologies, but the mechanisms by which they exert such diverse functions remain to be elucidated. A hallmark feature of mast cells is their remarkably high content of electron-dense secretory granules. These contain an array of bioactive compounds, of which various proteases (tryptase, chymase, CPA3) account for a major fraction. When addressing the function of these proteases, recent research has indicated that tryptase can have a hitherto unknown impact on various biological processes, including the proliferation of cancer cells and mast cells. Intriguingly, our recent findings suggest that tryptase accomplishes several of these functions after entering the nuclei of the target cell. The aim of this investigation is to pursue these findings by elucidating the underlying molecular mechanisms, including investigations of how tryptase is transported to the nucleus, how tryptase affects gene expression/proliferation and identification of nuclear substrates for tryptase. Moreover, we will use clinical samples to investigate the presence and subcellular location of tryptase in human tumors, and also assess the role of tryptase in other pathological contexts. Altogether, we believe that the project will generate knowledge that can enhance our understanding of how mast cells impact on disease settings, and we anticipate that such knowledge can be exploited for diagnostic and/or therapeutic purposes.