Cell surface complex of cathepsin B/annexin II tetramer in malignant progression

The cysteine protease cathepsin B is upregulated in a variety of tumors, pa rticularly at the invasive edges. Cathepsin B can degrade extracellular mat rix proteins, such as collagen IV and laminin, and can activate the precurs or form of urokinase plasminogen activator (uPA), perhaps thereby initiatin g an extracellular proteolytic cascade. Recently, we demonstrated that proc athepsin B interacts with the annexin II heterotetramer (AIIt) on the surfa ce of tumor cells. AIIt had previously been shown to interact with the seri ne proteases: plasminogen/plasmin and tissue-type plasminogen activator (tP A). The AIIt binding site for cathepsin B differs from that for either plas minogen/plasmin or tPA. AIIt also interacts with extracellular matrix prote ins, e.g., collagen I and tenascin-C, forming a structural link between the tumor cell surface and the extracellular matrix. Interestingly, cathepsin B, plasminogen/plasmin, t-PA and tenascin-C have all been linked to tumor d evelopment. We speculate that colocalization through AIIt of proteases and their substrates on the tumor cell surface may facilitate: (1) activation o f precursor forms of proteases and initiation of proteolytic cascades; and (2) selective degradation of extracellular matrix proteins. The recruitment of proteases to specific regions on the cell surface, regions where potent ial substrates are also bound, could well function as a 'proteolytic center ' to enhance tumor cell detachment, invasion and motility. (C) 2000 Elsevie r Science B.V. All rights reserved.