title: A novel monoclonal antibody to human laminin α5 chain strongly inhibits integrin-mediated cell adhesion and migration on laminins 511 and 521.
abstract: Laminins, a large family of αβγ heterotrimeric proteins mainly found in basement membranes, are strong promoters of adhesion and migration of multiple cell types, such as tumor and immune cells, via several integrin receptors. Among laminin α (LMα) chains, α5 displays the widest tissue distribution in adult life and is synthesized by most cell types. Here, we have generated and characterized five novel monoclonal antibodies (mAbs) to the human LMα5 chain to further study the biological relevance of α5 laminins, such as laminins 511 (α5β1γ1) and 521 (α5β2γ1). As detected by ELISA, immunohistochemistry, immunoprecipitation and Western blotting, each antibody displayed unique properties when compared to mAb 4C7, the prototype LMα5 antibody. Of greatest interest, mAb 8G9, but not any other antibody, strongly inhibited α3β1/α6β1 integrin-mediated adhesion and migration of glioma, melanoma, and carcinoma cells on laminin-511 and, together with mAb 4C7, on laminin-521. Accordingly, mAb 8G9 abolished the interaction of soluble α3β1 integrin with immobilized laminins 511 and 521. Binding of mAb 8G9 to laminin-511 was unaffected by the other mAbs to the LMα5 chain but largely hindered by mAb 4E10 to a LMβ1 chain epitope near the globular domain of laminin-511. Thus, mAb 8G9 defines a novel epitope localized at or near the integrin-binding globular domain of the LMα5 chain, which is essential for cell adhesion and migration, and identifies a potential therapeutic target in malignant and inflammatory diseases.
authors: Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Zenebech
authors: Z
authors: Wondimu
authors: Shahin
authors: S
authors: Omrani
authors: Taichi
authors: T
authors: Ishikawa
authors: Fawad
authors: F
authors: Javed
authors: Yuko
authors: Y
authors: Oikawa
authors: Ismo
authors: I
authors: Virtanen
authors: Erkki
authors: E
authors: Juronen
authors: Sulev
authors: S
authors: Ingerpuu
authors: Manuel
authors: M
authors: Patarroyo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D007797:Laminin / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D016023:Integrins; D007797:Laminin; C097043:laminin alpha5