Correlation between tumor proliferation and tumor tissue level of urokinase-type plasminogen activator

We established a xenotransplanted human colon cancer strain, TK-3, which produces urokinase-type plasminogen activator (U-PA) and carcinoembryonic antigen (CEA) simultaneously. Immunohistochemical staining of U-PA revealed that U-PA was located in the cytoplasm of cancer cells. Using TK-3, we investigated whether the tissue level of U-PA changed when the tumor proliferated locally. The mice were divided into three groups: mice of group A, B and C were sacrificed at 4, 5 and 6 weeks after tumor inoculation, respectively. The tissue level of U-PA was 0.78 +/- 0.183 ng/mg protein in group A, 0.95 +/- 0.189 in group B and 1.13 +/- 0.311 in group C. The values of groups B and C increased significantly compared with those of group A, and the tumor weight in each group showed a similar increase. The level of plasminogen activator inhibitor type 2 also increased (0.14 +/- 0.078 ng/mg protein in group A, 0.17 +/- 0.096 in group B, 0.24 +/- 0.172 in group C). On the other hand, the tissue level of CEA did not change significantly (78 micrograms/g tissue in group A, 88 in group B, 76 tissue in group C), and no correlation was observed between the tissue levels of U-PA and CEA. These results suggest that U-PA plays an important role not only in metastasis, but also in local tumor proliferation, and that its biological action in the autocrine system is independent of CEA.