title: Laminin-111-derived peptides and cancer.
abstract: Laminin-111 is a large trimeric basement membrane glycoprotein with many active sites. In particular, four peptides active in tumor malignancy studies have been identified in laminin-111 using a systematic peptide screening method followed by various assays. Two of the peptides (IKVAV and AG73) are found on the α1 chain, one (YIGSR) of the β1 chain and one (C16) on the γ1 chain. The four peptides have distinct activities and receptors. Since three of the peptides (IKVAV, AG73 and C16) strongly promote tumor growth, this may explain the potent effects laminin-111 has on malignant cells. The peptide, YIGSR, decreases tumor growth and experimental metastasis via a 32/67 kD receptor while IKVAV increases tumor growth, angiogenesis and protease activity via integrin receptors. AG73 increases tumor growth and metastases via syndecan receptors. C16 increases tumor growth and angiogenesis via integrins. Identification of such sites on laminin-111 will have use in defining strategies to develop therapeutics for cancer.
authors.affiliation: Laboratory of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Yamato
authors.initials: Y
authors.lastname: Kikkawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hozumi
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Katagiri
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Nomizu
authors.forename: Hynda K
authors.initials: HK
authors.lastname: Kleinman
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Koblinski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001485:Basement Membrane / Q000378:metabolism; D020134:Catalytic Domain; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism* / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding
chemical_list: C105786:AG 73; D000970:Antineoplastic Agents; D007797:Laminin; D009842:Oligopeptides; D010446:Peptide Fragments; C569383:aspartyl-phenylalanyl-lysyl-leucyl-phenylalanyl-alanyl-valyl-tyrosyl-isoleucyl-lysyl-tyrosyl-arginine; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine; C083321:isoleucyl-lysyl-valyl-alanyl-valine