Proteolysis in human breast cancer

Background-The process of proteolysis is important at several stages of the metastatic cascade. A balance between the expression of the genes encoding endogenous proteinases and inhibitors exists and when the production of pr oteinases exceeds that of inhibitors proteolysis occurs. Aims-To determine whether differences in the profile and activity of protei nases and inhibitors exist within breast tumour tissue (n = 51), surroundin g background breast tissue (n = 43), normal breast tissue from breast reduc tion mammoplasty operations (n = 10), and cells of the breast cancer cell l ine, MCF-7. Methods-Proteinase (matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-3, MMP-9 , urokinase-type plasminogen activator (uPA), and tissue-type PA (tPA)) and inhibitor (tissue inhibitor of metalloproteinases; TIMP-1 and TIMP-2) expr ession and proteinase activity were compared using substrate zymography, we stern blotting, immunohistochemistry, and quenched fluorescent substrate hy drolysis. Results-The presence of all proteinases and inhibitors was greater in breas t tumour tissue when compared with all other types of breast tissue (p < 0. 05). The activity of total MMMPs as determined by quenched fluorescent subs trate hydrolysis was also greater in breast tumours (p < 0.05). Conclusion-There is increased proteolysis in human breast tumours when comp ared with other breast tissues.