Detection of N-glycolyated gangliosides in non-small-cell lung cancer using GMR8 monoclonal antibody
Detection of N-glycolyated gangliosides in non-small-cell lung cancer using GMR8 monoclonal antibody
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DOI：
10.1111/cas.12027
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发表时间：
2013-01-01
期刊：
影响因子：
5.7
通讯作者：
Takahashi, Hiroki
中科院分区：
文献类型：
--
作者：
Hayashi, Nobuyoshi;Chiba, Hirofumi;Takahashi, Hiroki
神经节苷是在细胞表面发现的鞘脂糖。它们作为识别分子或信号调节剂，调节细胞的增殖和分化。含有n -糖基神经氨酸（NeuGc）的神经节苷在人类的一些肿瘤中被检测到，尽管它们通常在正常人体组织中不存在。我们的目的是评估含有NeuGc的神经节苷脂的存在，包括GM3 (NeuGc)，并评估它们与非小细胞肺癌（NSCLC）预后的关系。采用小鼠单克隆抗体GMR8免疫组织化学分析了NeuGc-含神经节苷脂在NSCLC组织中的表达，GMR8对NeuGc α 2,3gal末端结构的神经节苷脂具有特异性。在neugc含神经节苷脂表达的基础上，我们进行了生存分析。我们还研究了GM3 （n -乙酰神经氨酸[NeuAc]）和GM3 （NeuGc）对A431细胞表皮生长因子受体（EGFR）酪氨酸激酶抑制作用的差异。结果，在93例NSCLC样本中有86例（93.5%）存在neugc -神经节苷。neugc -神经节苷脂高表达的NSCLC患者总生存率较低，无进展生存率明显较低。在体外研究中，GM3对暴露于GM3 （NeuGc）后A431细胞EGFR酪氨酸激酶的抑制作用低于暴露于GM3 （NeuAc）后。综上所述，包括GM3 （NeuGc）在内的NeuGc-containing神经节苷脂在NSCLC中广泛表达，NeuGc-containing神经节苷脂的表达与患者生存率相关。GM3 （NeuGc）和GM3 （NeuAc）对EGFR酪氨酸激酶抑制作用的差异可能有助于改善NSCLC患者的预后。（癌症科学2013；104:4347）
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. (Cancer Sci 2013; 104: 4347)