Reduced pulmonary metastases of lewis lung carcinoma in hPAI-1 transgenic mice

Gene Manipulation and Transfer of the Plasminogen and Coagulation System in Mice

“…126 No significant effect on "spontaneous" pulmonary metastases of the Lewis lung carcinoma (3LL) cells was observed in transgenic mice overexpressing the aminoterminal fragment of u-PA. 47 PAI-1-overexpressing mice, injected intramuscularly with 3LL cells and treated with ZnSO 4 (which increased the activity of the metallothionein promoter that directs the human PAI-1 transgene), displayed a significant reduction of "spontaneous" pulmonary metastases with no effect on tumor growth. 127 Furthermore, formation of "artificial" lung nodules occurred at a reduced frequency in these mice. Since PAI-1 was localized to the endothelial lining of capillary vessels in the primary tumor and in the lungs of 3LL-bearing PAI-1 transgenic mice, reduced lodging of the 3LL tumor cells to the pulmonary vessels may explain the inhibition of metastatic spread.…”

“…Since PAI-1 was localized to the endothelial lining of capillary vessels in the primary tumor and in the lungs of 3LL-bearing PAI-1 transgenic mice, reduced lodging of the 3LL tumor cells to the pulmonary vessels may explain the inhibition of metastatic spread. 127 Recently, carcinogen-induced melanocytic neoplasms in u-PA-deficient mice were found to invade the underlying tissues at a reduced rate (Shapiro et al, personal communication). The use of knock-out mice and other models including crossbreeding with a tumor-developing transgenic mouse strain may provide means to further examine the role of the plasminogen system in malignancy.…”