Expression and localisation of urokinase-type plasminogen activator gene in gliomas

Urokinase-type plasminogen activator (uPA) activity is related to the malig nant biological behaviour of tumours. In the present study, we examined the presence and distribution of uPA in human gliomas. The amounts of uPA were measured by Northern blotting hybridisation and immunohistochemistry in 43 gliomas and five normal brain specimens. Their relation to the clinical hi story was comprehensively analysed. All tissues expressed 2.5 kb transcript s of uPA mRNA. The uPA mRNA levels were significantly higher in high grade gliomas than they were in low grade gliomas and normal brain tissue (P < 0. 01). Levels of uPA mRNA expression in tumour tissues with recurrence within 18 months postoperatively and survival less than 3 years were significantl y higher than counterparts (P < 0.01). The uPA mRNA was also expressed in t umour cells near necrotic areas. The uPA protein expression was consistent with the uPA mRNA expression. The distribution of uPA protein immunoreactiv ity was mainly in tumour cells and microvascular endothelial cells of gliob lastomas and anaplastic astrocytomas, localising in the cytoplasm, especial ly at sites of vascular proliferation and at the leading edges of tumours. These results suggest that expression of the uPA gene is associated with th e malignant progression of gliomas and may play an important role in the re currence and invasive behaviors of higher grade gliomas. (C) 2000 Harcourt Publishers Ltd.