title: Detection of N-glycolyated gangliosides in non-small-cell lung cancer using GMR8 monoclonal antibody.
abstract: Gangliosides are glycosphingolipids found on the cell surface. They act as recognition molecules or signal modulators and regulate cell proliferation and differentiation. N-glycolylneuraminic acid (NeuGc)-containing gangliosides have been detected in some neoplasms in humans, although they are usually absent in normal human tissues. Our aim was to evaluate the presence of NeuGc-containing gangliosides including GM3 (NeuGc) and assess their relationship with the prognosis of non-small-cell lung cancer (NSCLC). NeuGc-containing ganglioside expression in NSCLC tissues was analyzed immunohistochemically using the mouse monoclonal antibody GMR8, which is specific for gangliosides with NeuGc alpha 2,3Gal-terminal structures. On the basis of NeuGc-containing ganglioside expression, we performed survival analysis. We also investigated the differences in the effects of GM3 (N-acetylneuraminic acid [NeuAc]) and GM3 (NeuGc) on inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase in A431 cells. As a result, the presence of NeuGc-containing gangliosides was evident in 86 of 93 (93.5%) NSCLC samples. The NSCLC patients with high NeuGc-containing ganglioside expression had a low overall survival rate and a significantly low progression-free survival rate. In the in vitro study, the inhibitory effect of GM3 on EGFR tyrosine kinase in A431 cells after exposure to GM3 (NeuGc) was lower than that after exposure to GM3 (NeuAc). In conclusion, NeuGc-containing gangliosides including GM3 (NeuGc) are widely expressed in NSCLC, and NeuGc-containing ganglioside expression is associated with patient survival. The difference in the effects of GM3 (NeuGc) and GM3 (NeuAc) on the inhibition of EGFR tyrosine kinase might contribute to improvement in the prognosis of NSCLC patients.
authors.affiliation: Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hayashi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Chiba
authors.forename: Koji
authors.initials: K
authors.lastname: Kuronuma
authors.forename: Shinji
authors.initials: S
authors.lastname: Go
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Motoko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Shinsei
authors.initials: S
authors.lastname: Gasa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Watanabe
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kuroki
authors.forename: Jinichi
authors.initials: J
authors.lastname: Inokuchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D005679:G(M3) Ganglioside / Q000032:analysis; D005732:Gangliosides / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D006028:Glycosphingolipids / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000032:analysis*; D009438:Neuraminic Acids / Q000032:analysis*; D010766:Phosphorylation; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D005679:G(M3) Ganglioside; D005732:Gangliosides; D006028:Glycosphingolipids; D009438:Neuraminic Acids; C032592:N-glycolylneuraminic acid; D066246:ErbB Receptors; D019158:N-Acetylneuraminic Acid