The mast cell is best known for its harmful effects in allergy, but much research suggests that the mast cell also has an important and harmful role in cancer. However, very little is known about the exact mechanism of action of the mast cell. When the mast cell is activated, it releases a number of components that are normally stored inside the cell's so-called secretory granules, such as various protein-degrading enzymes (proteases) and growth factors. Together, these components could have major effects on a tumor, such as facilitating the tumor's blood supply, but there is only limited knowledge about this. We want to find out exactly how the mast cell affects cancer. To this end, we will compare tumor development and metastasis in normal mice and mice that either completely lack mast cells, or lack different mast cell components. We will also investigate the role of mast cells in blood vessel formation, and isolate and characterize tumor mast cells from lung cancer patients. Furthermore, we will develop a novel technique to induce mast cells to commit "suicide" and investigate whether this technique can be applied to mast cells in clinical tumors. Since there is now much research suggesting that the mast cell has a detrimental role in cancer, there is a strong case for developing new cancer therapies and diagnostics that target the mast cell, e.g. to be used in combination with existing therapies/diagnostics. We believe that this project can contribute to such developments.