Detection of N ‐glycolyated gangliosides in non‐small‐cell lung cancer using GMR 8 monoclonal antibody

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 ( N eu G c)‐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 N eu G c‐containing gangliosides including GM 3 ( N eu G c) and assess their relationship with the prognosis of non‐small‐cell lung cancer ( NSCLC ). Neu G c‐containing ganglioside expression in NSCLC tissues was analyzed immunohistochemically using the mouse monoclonal antibody GMR 8, which is specific for gangliosides with N eu G c alpha 2,3 G al‐terminal structures. On the basis of N eu G c‐containing ganglioside expression, we performed survival analysis. We also investigated the differences in the effects of GM 3 ( N ‐acetylneuraminic acid [ N eu A c]) and GM 3 ( N eu G c) on inhibition of epidermal growth factor receptor ( EGFR ) tyrosine kinase in A 431 cells. As a result, the presence of N eu G c‐containing gangliosides was evident in 86 of 93 (93.5%) NSCLC samples. The NSCLC patients with high N eu G c‐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 GM 3 on EGFR tyrosine kinase in A 431 cells after exposure to GM 3 ( N eu G c) was lower than that after exposure to GM 3 ( N eu A c). In conclusion, N eu G c‐containing gangliosides including GM 3 ( N eu G c) are widely expressed in NSCLC , and N eu G c‐containing ganglioside expression is associated with patient survival. The difference in the effects of GM 3 ( N eu G c) and GM 3 ( N eu A c) on the inhibition of EGFR tyrosine kinase might contribute to improvement in the prognosis of NSCLC patients. ( Cancer Sci 2013; 104: 43–47)