Urokinase and macrophages in tumour angiogenesis.

Recent studies have shown that elevated levels of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) in breast cancer correlate with an increased risk of a reduced relapse-free survival time and shortened overall survival times. Urokinase PA and PAI-1 are independent prognostic indicators for breast cancer. The fact that plasminogen activators are indispensable for tube formation of microvascular cells and that they may induce angiogenesis in vitro strongly suggests a role for uPA and PAI-1 in tumour neovascularisation. Because macrophages and tumour cells produce uPA, we postulate a close collaboration between tumour cells and tumour-associated macrophages in angiogenesis. To investigate how uPA levels and macrophage counts in tumour tissue correlate with angiogenesis, we counted microvessels and determined uPA levels and macrophage content in 42 primary invasive breast carcinomas. Using light microscopy, we highlighted the vessels by staining their endothelium cells immunocytochemically for CD31 and factor VIII and the macrophages for CD68. After obtaining tumour tissue extracts, we determined the uPA and PAI-1 levels by ELISA. A positive correlation between microvessel density, vascular invasion, uPA level, macrophage content and proliferation rate was found.