Elevated levels of urokinase-type plasminogen activator and its receptor during tumor growth in vivo

Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) are impo rtant in the regulation of tumor tissue progenesis, cell differentiation, t umor cell motility, and tumor cell invasiveness. We have recently reported that the levels of uPA and uPAR were higher in malignant astrocytomas than in low-grade gliomas. In the present study, we measured the levels of uPA a nd uPAR during the growth of glioblastomas in nude mice. Using fibrin zymog raphy, densitometry, and an enzyme-linked immunosorbent assay, we found tha t the enzyme activity and content of uPA were increased 4- to 10-fold durin g tumor formation. Using a receptor assay and an enzyme linked immunosorben t assay, we found the numbers and content of uPAR were increased 5- to 15-f old during tumor formation. In addition, immunohistochemical staining for u PA and uPAR revealed strong immunoreactivity in tumor cells with the staini ng more intense on day 28 than on day 14. These results suggest that the up regulation of uPA and uPAR plays a major role in the formation of gliomas.