We have produced mice that do not make mesothelin and are comparing them with normal mice to determine if various types of cancer will grow in the peritoneal cavity of these mice, where mesothelin is present on the mesothelial cells lining the peritoneal cavity of the normal mice. We have crossed these mice with immuno-deficient mice to make meso-/-, nu/nu mice to allow human cancer cells to grow in the peritoneal cavity of the mice. We find that a human lung cancer line grows more slowly in the peritoneal cavity of meso-/- mice than meso+/+ mice suggesting a role for mesothelin or MPF in tumor growth in the peritoneal cavity. We also found that injecting these mice with MPF enhances tumor growth. This is the first evidence that MPF has a biological role in cancer. In a second series of experiments we have tried to identify proteins that are associated with mesothelin. We have taken 2 approaches. One is to immuno-precipitate mesothelin from cells and determine which proteins are co-precipitated with it. The second is to investigate if mesothelin is located in subdomains of the plasma membranes like lipid rafts and the determine what other cell proteins are located in that region with mesothelin.
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