TUMOR PROGRESSION AND ANGIOGENESIS - CATHEPSIN-B AND CO

Experimental and clinical evidence reveals that the growth of solid tu mors is dependent on angiogenesis. Proteolytic enzymes such as plasmin ogen activators and matrix metalloproteinases have been implicated in this neovascularization. The role of lysosomal proteases in this proce ss has yet to be explored. Increased expression of the lysosomal cyste ine protease cathepsin B has been observed in many etiologically diffe rent tumors, including human brain, prostate, breast, and,gastrointest inal cancers. Immunohistochemical and in situ histochemical studies ha ve demonstrated expression of cathepsin B in neovessels induced during malignant progression of human glioblastoma and prostate carcinomas. In these two tumor types, neovessels stain strongly for cathepsin B co mpared with the normal microvasculature. As an initial point to elucid ate whether cathepsin B is an important component of the angiogenic re sponse in tumours, we analyzed expression of cathepsin B in endothelia l cells during neovessel formation. We present evidence for strong imm unostaining of cathepsin B in rat brain microvascular endothelial cell s as they form capillary tubes in vitro. This finding is discussed wit hin the general framework of the role of proteolytic enzymes in tumor invasion and angiogenesis.