title: A novel consensus motif in fibronectin mediates dipeptidyl peptidase IV adhesion and metastasis.
abstract: Lung endothelial dipeptidyl peptidase IV (DPPIV/CD26) is a vascular address for cancer cells decorated with cell-surface polymeric fibronectin (poly-FN). Here, we identified the DPPIV-binding sites in FN and examined the effect of binding site peptides on DPPIV/poly-FN adhesion and metastasis. Using proteolytic fragments and maltose-binding protein fusion proteins that together span full-length FN, we found DPPIV-binding sites in type III repeats 13, 14, and 15 (FNIII13, -14, and -15, respectively). DPPIV binding was mediated by the consensus motif T(I/L)TGLX(P/R)G(T/V)X and was confirmed by swapping this motif in FNIII13, -14, and -15 with the corresponding region in FNIII12, which did not bind DPPIV. DPPIV binding was lost in swapped FNIII13, -14, and -15 and gained in swapped FNIII12 (FNIII12(14)). Peptides containing the DPPIV-binding domain of FNIII14 blocked DPPIV/poly-FN adhesion and impeded pulmonary metastasis. This study adds to the classes of cell-surface adhesion receptors for FN and will help in the further characterization of the functional implications of the DPPIV/poly-FN adhesion in metastasis and possibly in cell-mediated immunity involving DPPIV-expressing lymphocytes.
authors.affiliation: Cancer Biology Laboratories, Department of Molecular Medicine, Cornell University College of Veterinary Medicine, Ithaca, New York 14853, USA.
authors.forename: Hung-Chi
authors.initials: HC
authors.lastname: Cheng
authors.forename: Mossaad
authors.initials: M
authors.lastname: Abdel-Ghany
authors.forename: Bendicht U
authors.initials: BU
authors.lastname: Pauli
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000235:genetics*; D011485:Protein Binding; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D005353:Fibronectins; D018819:Dipeptidyl Peptidase 4