Cysteine proteinases and their inhibitors in extracellular fluids: Markersfor diagnosis and prognosis in cancer

Cathepsins B, H and L have been shown to participate in processes of tumor growth, vascularization, invasion and metastasis. Their levels in tumor tis sue extracts can provide useful clinical information to predict disease-fre e and overall survival in breast, lung, colorectal, brain and head and neck cancer patients. Recently we have found that both cystine cathepsins and t heir endogenous protein inhibitors stefins and cystatin C cart also predict prognosis when measured extracellularly In melanoma and colorectal cancer patients high serum levels of cathepsins B and H correlated with shorter su rvival. Similarly, increased extracellular levels of stefins A and B and cy statin C cor-related significantly with high risk of adverse outcome in can cer patients. However, the cathepsin B/cystatin C complex was found to be l ess abundant in set-a of patients with malignant tumors than in those with benign diseases or ill healthy controls, suggesting an imbalance between th e enzyme and its inhibitor in cancer patients.