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 proteinases exceeds that of inhibitors proteolysis occurs. Aims-To determine whether differences in the profile and activity of proteinases and inhibitors exist within breast tumour tissue (n = 51), surrounding background breast tissue (n = 43), normal breast tissue from breast reduction mammoplasty operations (n = 10), and cells of the breast cancer cell line, 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) expression and proteinase activity were compared using substrate zymography, western blotting, immunohistochemistry, and quenched fluorescent substrate hydrolysis. Results-The presence of all proteinases and inhibitors was greater in breast tumour tissue when compared with all other types of breast tissue (p < 0.05). The activity of total MMMPs as determined by quenched fluorescent substrate hydrolysis was also greater in breast tumours (p < 0.05). Conclusion-There is increased proteolysis in human breast tumours when compared with other breast tissues.