Cysteine proteinases and their inhibitors in extracellular fluids: Markers for 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 tissue extracts can provide useful clinical information to predict disease-free and overall survival in breast, lung, colorectal, brain and head and neck cancer patients. Recently we have found that both cystine cathepsins and their 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 survival. Similarly, increased extracellular levels of stefins A and B and cystatin C cor-related significantly with high risk of adverse outcome in cancer patients. However, the cathepsin B/cystatin C complex was found to be less abundant in set-a of patients with malignant tumors than in those with benign diseases or ill healthy controls, suggesting an imbalance between the enzyme and its inhibitor in cancer patients.