title: Laminins 411 and 421 differentially promote tumor cell migration via α6β1 integrin and MCAM (CD146).
abstract: α4-laminins, such as laminins 411 and 421, are mesenchymal laminins expressed by blood and lymphatic vessels and some tumor cells. Laminin-411 promotes migration of leukocytes and endothelial cells, but the effect of this laminin and laminin-421 on tumor cells is poorly understood. In the present study, we demonstrate that laminin-411 and, to a greater extent, laminin-421 significantly promote migration of tumor cells originated from melanomas, gliomas and different carcinomas via α6β1 integrin. In solid-phase binding assays, both laminins similarly bound α6β1 integrin but only laminin-421, among several laminin isoforms, readily bound MCAM (CD146), a cell-surface adhesion molecule strongly associated with tumor progression. Accordingly, a function-blocking mAb to MCAM inhibited tumor cell migration on laminin-421 but not on laminins 411 or 521. In tumor tissues, melanoma cells co-expressed MCAM, laminin α4, β1, β2 and γ1 chains, and integrin α6 and β1 chains. The present data highlight the novel role of α4-laminins in tumor cell migration and identify laminin-421 as a primary ligand for MCAM and a putative mediator of tumor invasion and metastasis.
authors.affiliation: Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Taichi
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Zenebech
authors.initials: Z
authors.lastname: Wondimu
authors.affiliation: Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Oikawa
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Giusy
authors.initials: G
authors.lastname: Gentilcore
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rolf
authors.initials: R
authors.lastname: Kiessling
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Egyhazi Brage
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Hansson
authors.affiliation: Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: Manuel.Patarroyo@ki.se.
authors.forename: Manuel
authors.initials: M
authors.lastname: Patarroyo
mesh_terms: D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000276:immunology; D051929:CD146 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D039121:Integrin alpha6beta1 / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D009369:Neoplasms / Q000503:physiopathology*
chemical_list: D000911:Antibodies, Monoclonal; D051929:CD146 Antigen; D039121:Integrin alpha6beta1; C501369:LAMA4 protein, human; D007797:Laminin; C497902:MCAM protein, human
keywords: CD146; Cell migration; Integrin; Laminin; MCAM