Title:	SEPRASE-DPPIV ASSOCIATION FOR PROLYL PEPTIDASE AND GELATINASE ACTIVITIES
Authors:	G. Ghersi1, H. Dong2, L.A. Goldstein2, Y. Yeh2, L. Hakkinen3, H.S. Larjava3 and W-T. Chen2 1 Department of Cellular and Developmantal Biology, University of Palermo, Viale delle scienze 90138 Palermo, Italy. 2 Department of Medicine/Medical Oncology, State University of New York, Stony Brook New York 11794 8154, USA. 3 University of British Columbia, Division of Periodontics, 2199 Westbrook Mall, Vancouver, BC V6T 1Z3, CANADA.
Presented At:	International Conference on Dipeptidyl Aminopeptidases - Basic and Clinical Applications, Berlin, Germany
Date Presented:	September 26-29, 2002
Abstract
Cell migration is driving by the action of proteolytic enzymes on the cell surface that permits cell movement and invasion into the extracellular matrix (ECM). Both metallo- and serine proteases are involved in these processes. Here we show that seprase and dipeptidyl peptidase IV (DPPIV), both membrane-bound prolyl peptidases, form a novel complex at invadopodia of migratory fibroblast in collagenous ECM substrata and formation of the protease complex is a prerequisite in cell invasion and migration. The protease complex elicits both gelatin-binding and gelatinase activities localized at invadopodia of cells migrating on and invading in collagenous fibers. The binding to gelatin, the localized gelatin degradation, cellular migration, and invasion in collagen gel were inhibited by prolyl peptidase inhibitors and specific mAbs against the gelatin-binding domain of DPPIV. Moreover, these mAbs reduce cellular ability to degrade gelatin but do not affect cellular adhesion or spreading on type I collagen. Consistently, expression of the seprase-DPPIV complex is restricted to migratory cells involved in wound closure in vitro, and in connective tissue cells during closure of gingival wounds and carcinoma invasion, but not in differentiated tissues.