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Báo cáo khoa học: Epitope analysis of the rat dipeptidyl peptidase IV monoclonal antibody 6A3 that blocks pericellular fibronectin-mediated cancer cell adhesion

We previously showed that the rat dipeptidyl peptidase IV (rDPP IV) monoclonal antibody (mAb) 6A3 greatly inhibits the pericellular polymeric fibronectin-mediated metastatic cancer cell adhesion to rDPP IV. L 311 QWLRRI in rDPP IV has been proposed as the putative fibronectin-binding site. | ễFEBS Journal Epitope analysis of the rat dipeptidyl peptidase IV monoclonal antibody 6A3 that blocks pericellular fibronectin-mediated cancer cell adhesion Ting-Ting Hung1 Jun-Yi Wu1 Ju-Fang Liu1 and Hung-Chi Cheng1 2 1 Department of Biochemistry and Molecular Biology College of Medicine NationalCheng Kung University Tainan Taiwan 2 NationalCheng Kung University HospitalCancer Center NationalCheng Kung University Tainan Taiwan Keywords dipeptidylpeptidase IV epitope mapping monoclonalantibody polymeric fibronectin steric hindrance Correspondence H.-C. Cheng Department of Biochemistry and Molecular Biology College of Medicine NationalCheng Kung University Tainan 70101 Taiwan Fax 886 6 274 1694 Tel 886 6 235353 E-mail hungchi@mail.ncku.edu.tw These authors contributed equally to this work. Received 9 June 2009 revised 27 July 2009 accepted 3 September 2009 doi 10.1111 j.1742-4658.2009.07352.x We previously showed that the rat dipeptidyl peptidase IV rDPP IV monoclonal antibody mAb 6A3 greatly inhibits the pericellular polymeric fibronectin-mediated metastatic cancer cell adhesion to rDPP IV. L311QWLRRI in rDPP IV has been proposed as the putative fibronectin-binding site. However the inhibitory mechanism of 6A3 has been elusive. Epitope mapping of 6A3 may help to understand the interaction between fibronectin and rDPP IV. In the present study we showed that 6A3 spe-cies-specifically recognized rDPP IV but inhibited Íibronectin TDPP IV-mediated cell adhesions of various cancer types and species which was independent of rDPP IV enzymatic activity. The 6A3 epitope was stably exposed in both native and denatured rDPP IV. On the basis of the resolved structures and the species variations in DPP IV sequences we finely mapped the 6A3 epitope to a surface-exposed Thr331-dependent motif D329KTTLVWN only 11 amino acids away from L311QWLRRI on the same plane as the fifth b-propeller blade. The functionality of 6A3 epitope in rDPP IV was ultimately demonstrated by the ability .