title: Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts.
abstract: BACKGROUND
  Emmprin, a glycoprotein containing two Ig domains, is enriched on tumor cell surfaces and stimulates matrix metalloproteinase (MMP) production by adjacent stromal cells. Its first Ig domain (ECI) contains the biologically active site. The dependence of emmprin activity on N-glycosylation is controversial. We investigated whether synthetic ECI with the shortest sugar is functionally active.
  
  
  METHODS
  The whole ECI peptides carrying sugar chains, a chitobiose unit or N-linked core pentasaccharide, were synthesized by the thioester method and added to fibroblasts to examine whether they stimulate MMP-2 production.
  
  
  RESULTS
  ECI carrying a chitobiose unit, ECI-(GlcNAc) 2, but not ECI without a chitobiose unit or the chitobiose unit alone, dose-dependently stimulated MMP-2 production by fibroblasts. ECI with longer chitobiose units, ECI-[(Man)3(GlcNAc)2], also stimulated MMP-2 production, but the extent of its stimulation was lower than that of ECI-(GlcNAc)2.
  
  
  CONCLUSIONS
  Our results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.
authors.affiliation: Department of Pathology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Takehito
authors.initials: T
authors.lastname: Kawakami
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sameshima
authors.forename: Hironobu
authors.initials: H
authors.lastname: Hojo
authors.forename: Kaori
authors.initials: K
authors.lastname: Koga
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nakahara
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Toole
authors.forename: Junji
authors.initials: J
authors.lastname: Suzumiya
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
authors.forename: Akinori
authors.initials: A
authors.lastname: Iwasaki
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nabeshima
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry; D000230:Adenocarcinoma / Q000473:pathology / Q000556:secondary; D000328:Adult; D051926:Basigin / Q000737:chemistry / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D002528:Cerebellar Neoplasms / Q000473:pathology / Q000556:secondary; D018920:Coculture Techniques; D004187:Disaccharides / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005208:Fasciitis / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D006031:Glycosylation; D006801:Humans; D008175:Lung Neoplasms; D008351:Mannans / Q000737:chemistry; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012509:Sarcoma / Q000473:pathology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C497886:BSG protein, human; D004187:Disaccharides; D008351:Mannans; D010446:Peptide Fragments; D051926:Basigin; C097323:polymannose; C032438:chitobiose; D020778:Matrix Metalloproteinase 2; D000117:Acetylglucosamine