Modulation of matrix metalloprotease-2 and invasion in human glioma cells by alpha 3 beta 1 integrin.
We have investigated the effect of integrin antibodies to a well-characterized alpha 5 beta 1 (fibronectin receptor) and to a multi-specific alpha 3 beta 1 (laminin, collagen, and fibronectin receptor), on the expression of matrix metalloproteases and the invasion ability of two human glioblastoma cell lines, SNB19 and U251. Cell adhesion assays indicated that both cell lines adhere to fibronectin, type IV collagen and laminin. Adhesion of cells to fibronectin was inhibited by a RGD peptide. Cells treated with anti-alpha 3 beta 1 or anti-alpha 5 beta 1 antibodies expressed increased levels of MMP-2. An in vitro matrigel assay also showed that the alpha 3 beta 1 antibody-treated cells had greater invasive ability than the controls. Immunofluorescence data showed that glioma cells treated with either anti-alpha 3 beta 1 or anti-alpha 5 beta 1 antibodies expressed diminished alpha 3 beta-1 and alpha 5 beta 1 integrins relative to the controls. The data show that treatment of cells with alpha 3 beta 1 antibody diminishes the integrin expression on the cell surface and increases the MMP-2 activity and invasiveness.
Chintala
S K
SK
Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Sawaya
R
R
Gokaslan
Z L
ZL
Rao
J S
JS
D002448:Cell Adhesion; D003094:Collagen; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D018093:Gelatinases / Q000378:metabolism; D005910:Glioma / Q000473:pathology*; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000378:metabolism*; D007797:Laminin; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011509:Proteoglycans; D017469:Receptors, Fibronectin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D016326:Extracellular Matrix Proteins; D039201:Integrin alpha3beta1; D016023:Integrins; D007797:Laminin; D011509:Proteoglycans; D017469:Receptors, Fibronectin; C059485:matrigel; D003094:Collagen; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2