Detection of a hypersialylated beta1 integrin endogenously expressed in the human astrocytoma cell line A172.
Gliomas are the most common deadly brain tumors. Human cerebral tumors express high level of alpha5beta1 integrins. As a potential new target, alpha5beta1 was investigated here in two human astrocytoma cell lines, A172 and U87MG. We found that a hypersialylated beta1 integrin was endogenously expressed in A172 cells. It forms heterodimers with alpha5 subunits, localizes at the cell membrane and allows adhesion to fibronectin. This form of beta1 integrin was only recognized by the 9EG7 anti-beta1 antibody and appeared devoid of other specific antibody epitopes (12G10, TS2/16 and mAb13 shown here to be N-glycosylation sensitive). Overexpression of the beta1 integrin subunit in A172 cells not only increased the hypersialylated form but also led to the appearance of a non-hypersialylated beta1 form also addressed to the cell surface. Compared to wild-type A172 cells, beta1-A172 cells showed increased adhesion to fibronectin and decreased sensitivity to SJ749, a non-peptidic alpha5beta1 antagonist. In addition, beta1-A172 cells exhibited increased matrix dependence for normal cell cycling. Collectively, the data add new evidence for the role of beta1 glycosylation/sialylation in the regulation of integrin functions.
Bartik
Petr
P
Département de Pharmacologie et Physicochimie, UMR 7175 CNRS, Université Louis Pasteur-Strasbourg I, Faculté de Pharmacie, BP 60024, 67401 Illkirch, France.
Maglott
Anne
A
Entlicher
Gustav
G
Vestweber
Dietmar
D
Takeda
Ken
K
Martin
Sophie
S
Dontenwill
Monique
M
D001254:Astrocytoma / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D019281:Dimerization; D005353:Fibronectins / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D039482:Integrin alpha5 / Q000378:metabolism; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D011725:Pyridines / Q000494:pharmacology; D012794:Sialic Acids / Q000378:metabolism*; D013141:Spiro Compounds / Q000494:pharmacology; D014162:Transfection; D015854:Up-Regulation
D005353:Fibronectins; D039482:Integrin alpha5; D039081:Integrin alpha5beta1; D019012:Integrin beta1; D011422:Propionates; D011725:Pyridines; C512312:SJ749; D012794:Sialic Acids; D013141:Spiro Compounds