title: Glioma cell dispersion is driven by α5 integrin-mediated cell-matrix and cell-cell interactions.
abstract: Glioblastoma multiform (GBM) is the most common and most aggressive primary brain tumor. The fibronectin receptor, α5 integrin is a pertinent novel therapeutic target. Despite numerous data showing that α5 integrin support tumor cell migration and invasion, it has been reported that α5 integrin can also limit cell dispersion by increasing cell-cell interaction. In this study, we showed that α5 integrin was involved in cell-cell interaction and gliomasphere formation. α5-mediated cell-cell cohesion limited cell dispersion from spheroids in fibronectin-poor microenvironment. However, in fibronectin-rich microenvironment, α5 integrin promoted cell dispersion. Ligand-occupied α5 integrin and fibronectin were distributed in fibril-like pattern at cell-cell junction of evading cells, forming cell-cell fibrillar adhesions. Activated focal adhesion kinase was not present in these adhesions but was progressively relocalized with α5 integrin as cell migrates away from the spheroids. α5 integrin function in GBM appears to be more complex than previously suspected. As GBM overexpressed fibronectin, it is most likely that in vivo, α5-mediated dissemination from the tumor mass overrides α5-mediated tumor cell cohesion. In this respect, α5-integrin antagonists may be useful to limit GBM invasion in brain parenchyma.
authors.affiliation: Integrins and Cancer, Faculté de Pharmacie, UMR7213 CNRS, LBP, Tumoral Signaling and Therapeutic Targets Department, Université de Strasbourg, Illkirch, France.
authors.forename: Anne-Florence
authors.initials: AF
authors.lastname: Blandin
authors.affiliation: Integrins and Cancer, Faculté de Pharmacie, UMR7213 CNRS, LBP, Tumoral Signaling and Therapeutic Targets Department, Université de Strasbourg, Illkirch, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Noulet
authors.affiliation: Integrins and Cancer, Faculté de Pharmacie, UMR7213 CNRS, LBP, Tumoral Signaling and Therapeutic Targets Department, Université de Strasbourg, Illkirch, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Renner
authors.affiliation: Integrins and Cancer, Faculté de Pharmacie, UMR7213 CNRS, LBP, Tumoral Signaling and Therapeutic Targets Department, Université de Strasbourg, Illkirch, France.
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Mercier
authors.affiliation: Integrins and Cancer, Faculté de Pharmacie, UMR7213 CNRS, LBP, Tumoral Signaling and Therapeutic Targets Department, Université de Strasbourg, Illkirch, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Choulier
authors.affiliation: Integrins and Cancer, Faculté de Pharmacie, UMR7213 CNRS, LBP, Tumoral Signaling and Therapeutic Targets Department, Université de Strasbourg, Illkirch, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Vauchelles
authors.affiliation: Integrins and Cancer, Faculté de Pharmacie, UMR7213 CNRS, LBP, Tumoral Signaling and Therapeutic Targets Department, Université de Strasbourg, Illkirch, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ronde
authors.affiliation: Equipe de Recherche sur les Relations Matrice Extracellulaire Cellules, ERRMECe (EA 1391), Institut des Matériaux, Université de Cergy-Pontoise, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Carreiras
authors.affiliation: Integrins and Cancer, Faculté de Pharmacie, UMR7213 CNRS, LBP, Tumoral Signaling and Therapeutic Targets Department, Université de Strasbourg, Illkirch, France; Department of Pharmacy, Centre Paul Strauss, Strasbourg, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Etienne-Selloum
authors.affiliation: Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Hungary.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Vereb
authors.affiliation: Integrins and Cancer, Faculté de Pharmacie, UMR7213 CNRS, LBP, Tumoral Signaling and Therapeutic Targets Department, Université de Strasbourg, Illkirch, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lelong-Rebel
authors.affiliation: Integrins and Cancer, Faculté de Pharmacie, UMR7213 CNRS, LBP, Tumoral Signaling and Therapeutic Targets Department, Université de Strasbourg, Illkirch, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Martin
authors.affiliation: Integrins and Cancer, Faculté de Pharmacie, UMR7213 CNRS, LBP, Tumoral Signaling and Therapeutic Targets Department, Université de Strasbourg, Illkirch, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Dontenwill
authors.affiliation: Integrins and Cancer, Faculté de Pharmacie, UMR7213 CNRS, LBP, Tumoral Signaling and Therapeutic Targets Department, Université de Strasbourg, Illkirch, France. Electronic address: Maxime.lehmann@unistra.fr.
authors.forename: Maxime
authors.initials: M
authors.lastname: Lehmann
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002450:Cell Communication; D045744:Cell Line, Tumor; D002465:Cell Movement; D021982:Cell-Matrix Junctions / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D039564:Integrin alphaV / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D015398:Signal Transduction; D018874:Spheroids, Cellular; D013997:Time Factors; D014162:Transfection
chemical_list: D005353:Fibronectins; D039564:Integrin alphaV; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: Fibronectin; Focal adhesion kinase; Glioblastoma; Integrin; Migration