Cathepsin B and cystatins: evidence for a role in cancer progression.
The cysteine proteinase cathepsin B has been implicated in the progression of tumors from a premalignant to a malignant state. Activity of cathepsin B has been shown to be elevated in parallel with malignancy or metastatic potential of human and rodent tumors. These increases in cathepsin B activity correspond in part to increases in mRNA for cathepsin B and in part to reduced regulation by endogenous low Mr cysteine proteinase inhibitors. Most properties of tumor cathepsin B appear to be similar to those of cathepsin B from normal tissues. However, the subcellular distribution of cathepsin B is altered in tumors, resulting in association of cathepsin B with plasma membrane fractions or in release of high Mr forms of cathepsin B into the extracellular milieu. Since cathepsin B can degrade laminin, fibronectin and type IV collagen, we speculate that the presence of cathepsin B at the surface of tumor cells may contribute to the local dissolution of basement membrane observed during tumor cell extravasation. Direct evidence that cathepsin B plays a role in cancer progression awaits studies in which upregulation or downregulation of the expression of cathepsin B and its endogenous inhibitors is found to alter tumorigenesis, metastatic potential, etc.
Sloane
B F
BF
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201.
D000818:Animals; D002401:Cathepsin B / Q000502:physiology*; D015891:Cystatins / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009362:Neoplasm Metastasis / Q000503:physiopathology; D009369:Neoplasms / Q000201:enzymology*
D015891:Cystatins; D002401:Cathepsin B