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 isolated pancreatic cancer cells and stomach cancer cells with low mesothelin expression and found these cells are less tumorigenic than cells with high mesothelin levels suggesting a role for mesothelin in cancer progression in some types of tumors.
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