title: Molecular characterization of cell substratum attachments in human glial tumors relates to prognostic features.
abstract: Glioma cell attachments to substratum play crucial roles in the invasion by glioma cells of normal brain tissue. These attachments are mediated through interactions between extracellular matrix (ECM) components, integrins, focal adhesion-linked molecules, and the actin cytoskeleton. In the present study, we investigate the molecular elements involved in cell substratum attachments in human glial tumors and their potential relationships to prognostic features. We used 10 human glioma cell lines, for which we characterized glial differentiation by means of quantitative RT-PCR for nestin, vimentin, and GFAP mRNA. We quantitatively determined the amounts of laminin, fibronectin, vitronectin, and thrombospondin secreted by these glioma cell lines in vitro, as well as the amount of each of the eight beta integrin subunits and the adhesion complex-related molecules, including talin, vinculin, profilin, zyxin, alpha-actinin, paxillin, and VASP. After quantification of the levels of migration and invasion of these 10 cell lines in vitro and, through grafts into the brains of nude mice, of their biological aggressiveness in vivo, it appeared that the levels of the beta 5 integrin subunit and alpha-actinin were directly related to biological aggressiveness. These experimental data were clinically confirmed because increasing immunohistochemical amounts of the beta 5 integrin subunit and alpha-actinin were directly related to dismal prognoses in the case of astrocytic tumors. In addition, we show that the beta 4 integrin subunit are expressed significantly more in oligodendrogliomas than in astrocytic tumors. A potential role for the beta 8 integrin subunit in glioma cell substratum attachments is also emphasized.
authors.affiliation: Laboratory of Histopathology, Faculty of Medicine, Free University of Brussels, Brussels, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Belot
authors.forename: S
authors.initials: S
authors.lastname: Rorive
authors.forename: I
authors.initials: I
authors.lastname: Doyen
authors.forename: F
authors.initials: F
authors.lastname: Lefranc
authors.forename: E
authors.initials: E
authors.lastname: Bruyneel
authors.forename: R
authors.initials: R
authors.lastname: Dedecker
authors.forename: S
authors.initials: S
authors.lastname: Micik
authors.forename: J
authors.initials: J
authors.lastname: Brotchi
authors.forename: C
authors.initials: C
authors.lastname: Decaestecker
authors.forename: I
authors.initials: I
authors.lastname: Salmon
authors.forename: R
authors.initials: R
authors.lastname: Kiss
authors.forename: I
authors.initials: I
authors.lastname: Camby
mesh_terms: D000185:Actinin / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules; D019070:Cell Lineage / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D039641:Integrin beta Chains; D039663:Integrin beta4; D016023:Integrins / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology*; D009419:Nerve Tissue Proteins; D064231:Nestin; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D005904:Glial Fibrillary Acidic Protein; D039641:Integrin beta Chains; D039663:Integrin beta4; D016023:Integrins; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D014746:Vimentin; C084344:integrin beta5; D000185:Actinin