UROKINASE PLASMINOGEN-ACTIVATOR INDUCES ANGIOGENESIS AND TUMOR VESSEL INVASION IN BREAST-CANCER

Urokinase plasminogen activator (uPA) is a proteolytic enzyme implicated in cancer invasion and tumor progression. Urokinase PA and its inhibitor (PAI-1) appear to be new and independent prognostic markers in breast cancer. To investigate how uPA- and PAI-1-levels correlate with angiogenesis and tumor vessel invasion, we counted microvessels and their tumor invasion and determined the uPA- and PAI-1 levels in 42 primary invasive breast carcinomas. 20 Patients had no lymph node metastasis at the time of surgery, while 22 patients had positive nodes. Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocytochemically for CD31 and Factor VIII. After gaining tumor tissue extracts, we determined the uPA- and PAI-1-levels by ELISA. A positive correlation between microvessel density, angioinvasion and uPA- and PAI-1-levels was found. We speculate that high uPA levels may induce tumor neovascularisation, angioinvasion and may cause tumor progression and metastasis. The degradation of the vessel wall by uPA causes a leak. This wall defect may, on the one hand, be the stimulus for endothelial cell proliferation and formation of new blood vessels and, on the other hand it may be the place of tumor cell entry.