Lysosomal
cysteine proteinases, also known as
cysteine cathepsins (Cats), belong to the
papain family of
proteinases, and share a similar
protein structure and mechanism of action. However, subtle structural differences between these
cathepsins, e.g. Cats B, H and L, give rise to potentially important variations in substrate specificity and differences in inhibition by their endogenous inhibitors, the
cystatins,
stefins and
kininogens, under physiological and pathological conditions. Alterations in expression of Cat B and Cat L have been observed at various levels in malignant human
tumor tissue compared to normal and benign tissue counterparts. We proposed that an imbalance between
cathepsins and
cystatins, associated with the metastatic
tumor cell phenotype, may facilitate
tumor cell invasion and
metastasis and be responsible for early relapse of the disease after removal of the primary
tumor. The results of our initial investigations on
cysteine cathepsins and their endogenous inhibitors in human breast, lung and head and neck
carcinomas, as well as in body fluids of
melanoma and
colorectal carcinoma bearing patients, have indeed shown their high prognostic impact for the survival of these patients.