Cell surface complex of cathepsin B/annexin II tetramer in malignant progression.
The cysteine protease cathepsin B is upregulated in a variety of tumors, particularly at the invasive edges. Cathepsin B can degrade extracellular matrix proteins, such as collagen IV and laminin, and can activate the precursor form of urokinase plasminogen activator (uPA), perhaps thereby initiating an extracellular proteolytic cascade. Recently, we demonstrated that procathepsin B interacts with the annexin II heterotetramer (AIIt) on the surface of tumor cells. AIIt had previously been shown to interact with the serine proteases: plasminogen/plasmin and tissue-type plasminogen activator (tPA). The AIIt binding site for cathepsin B differs from that for either plasminogen/plasmin or tPA. AIIt also interacts with extracellular matrix proteins, 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 development. We speculate that colocalization through AIIt of proteases and their substrates on the tumor cell surface may facilitate: (1) activation of 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 potential substrates are also bound, could well function as a 'proteolytic center' to enhance tumor cell detachment, invasion and motility.
Mai
J
J
Department of Pharmacology, Wayne State University, School of Medicine, 540 East Canfield, Detroit, MI 48201, USA.
Waisman
D M
DM
Sloane
B F
BF
D000818:Animals; D017306:Annexin A2 / Q000737:chemistry / Q000378:metabolism*; D002401:Cathepsin B / Q000737:chemistry / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D017306:Annexin A2; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; D002401:Cathepsin B