title: Laminin isoforms and their integrin receptors in glioma cell migration and invasiveness: Evidence for a role of alpha5-laminin(s) and alpha3beta1 integrin.
abstract: Glioma cell infiltration of brain tissue often occurs along the basement membrane (BM) of blood vessels. In the present study we have investigated the role of laminins, major structural components of BMs and strong promoters of cell migration. Immunohistochemical studies of glioma tumor tissue demonstrated expression of alpha2-, alpha3-, alpha4- and alpha5-, but not alpha1-, laminins by the tumor vasculature. In functional assays, alpha3 (Lm-332/laminin-5)- and alpha5 (Lm-511/laminin-10)-laminins strongly promoted migration of all glioma cell lines tested. alpha1-Laminin (Lm-111/laminin-1) displayed lower activity, whereas alpha2 (Lm-211/laminin-2)- and alpha4 (Lm-411/laminin-8)-laminins were practically inactive. Global integrin phenotyping identified alpha3beta1 as the most abundant integrin in all the glioma cell lines, and this laminin-binding integrin exclusively or largely mediate the cell migration. Moreover, pretreatment of U251 glioma cells with blocking antibodies to alpha3beta1 integrin followed by intracerebral injection into nude mice inhibited invasion of the tumor cells into the brain tissue. The cell lines secreted Lm-211, Lm-411 and Lm-511, at different ratios. The results indicate that glioma cells secrete alpha2-, alpha4- and alpha5-laminins and that alpha3- and alpha5-laminins, found in brain vasculature, selectively promote glioma cell migration. They identify alpha3beta1 as the predominant integrin and laminin receptor in glioma cells, and as a brain invasion-mediating integrin.
authors: Department of Odontology and Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S 141 04 Stockholm, Sweden.
authors: Tomoyuki
authors: T
authors: Kawataki
authors: Tetsu
authors: T
authors: Yamane
authors: Hirofumi
authors: H
authors: Naganuma
authors: Patricia
authors: P
authors: Rousselle
authors: Ingegerd
authors: I
authors: Andurén
authors: Karl
authors: K
authors: Tryggvason
authors: Manuel
authors: M
authors: Patarroyo
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism*; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017474:Receptors, Laminin / Q000378:metabolism*
chemical_list: D019138:Antibodies, Blocking; D039201:Integrin alpha3beta1; D007797:Laminin; D020033:Protein Isoforms; D017474:Receptors, Laminin; C097043:laminin alpha5