Stimulation of glioma‐cell migration by laminin and inhibition by anti‐α3 and anti‐β1 integrin antibodies

• Published in: International journal of cancer Vol. 67; no. 6; pp. 777 - 784
• Main Authors: Tysnes, Berit B., Larsen, Lone F., Ness, Gro O., Mahesparan, Rupavathana, Edvardsen, Klaus, Garcia‐Cabrera, Inmaculada, Bjerkvig, Rolf
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 17-09-1996; Wiley-Liss
• Subjects: Biological and medical sciences; Medical sciences; Neurology; Tumors of the nervous system. Phacomatoses; Human; Nervous system diseases; Beta-Peptide chain; Cell adhesion molecule; Glycoproteins; Malignant tumor; Metastasis; In vitro; Binding protein; Malignant glioma; Membrane receptor; Integrin; Laminin; Dissemination; Central nervous system disease; Established cell line; Alpha-Peptide chain; Extracellular matrix
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19960917)67:6<777::AID-IJC5>3.0.CO;2-O

An induction of laminin in the confrontation zone between tumor cells and normal brain tissue has been observed in our model systems in vivo and in vitro. In order to study the effects of ECM components on glioma‐cell migration and invasion, we have used 2 lacZ‐transfected glioma cell lines, ANI/lacZ and U‐251/lacZ. Cell migration from multicellular spheroids was studied using different types of media: DMEM with 10% serum, Ultra Culture medium, and filtrated DMEM with serum in which the protein fraction > 100 kDa had been removed by ultrafiltration. Laminin, fibronectin and collagen type‐IV were individually added to the different media, and cell migration from the spheroids was studied. The results show that cell migration in both cell lines, was stimulated by laminin and fibronectin. Collagen type‐IV stimulated only cell migration of U‐251/lacZ cells. Scanning electron microscopy revealed an extensive change in cell shape as a result of laminin stimulation. Flow‐cytometric studies showed that both ANI/lacZ and U‐251/lacZ strongly express the α3β1 integrin receptor, which can bind to several ECM components (laminin, fibronectin, collagen). Immunofluorescence microscopy demonstrated that the same integrin sub‐units were expressed in multicellular spheroids. When monoclonal antibodies to α3 and β1 were added to the laminin‐stimulated cultures, cell migration was significantly reduced. This indicates that the α3β1 integrin receptor plays an important role during glioma‐cell migration. © 1996 Wiley‐Liss, Inc.