title: Synthetic emmprin peptides inhibit tumor cell-fibroblast interaction-stimulated upregulation of MMP-2 and tumor cell invasion.
abstract: Stromal cells are the main source of matrix metalloproteinases (MMPs) in human carcinoma tissues. Emmprin is a glycosylated transmembrane protein containing two immunoglobulin (Ig) domains that is expressed in carcinoma cells and stimulates MMP production by adjacent stromal cells. The first Ig domain (ECI) of emmprin contains the biologically active site. We investigated whether synthetic peptides carrying a partial ECI sequence could inhibit emmprin activity. Only the second peptide (emp#2), which contains a putative N-glycosylation site sequence, inhibited emmprin-stimulated production of MMP-2 in co-cultures of fibroblasts and several different human tumor cells types, including carcinoma, sarcoma, melanoma, leukemia and glioma cells. Moreover, emp#2 significantly inhibited the invasive activity of glioblastoma cells promoted by interaction with fibroblasts. Perturbation of emmprin activity by this peptide may have potential therapeutic uses in the prevention of MMP-2-dependent cancer invasion.
authors.affiliation: Department of Pathology, Fukuoka University Hospital , 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814‑0180, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Koga
authors.forename: Mikiko
authors.initials: M
authors.lastname: Aoki
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sameshima
authors.forename: Makoto
authors.initials: M
authors.lastname: Hamasaki
authors.forename: Nagayasu
authors.initials: N
authors.lastname: Egawa
authors.forename: Motoharu
authors.initials: M
authors.lastname: Seiki
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Toole
authors.forename: Junji
authors.initials: J
authors.lastname: Suzumiya
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nabeshima
mesh_terms: D000595:Amino Acid Sequence; D051926:Basigin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology*; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D010446:Peptide Fragments; D051926:Basigin; D020778:Matrix Metalloproteinase 2