Institute of Medical Physics and Biophysics, University of Münster, Germany.
Glycobiology. 2011 May;21(5):584-94. doi: 10.1093/glycob/cwq200. Epub 2010 Dec 7.
The sialic acid-specific cytotoxic lectin viscumin and its recombinant equivalent rViscumin specifically bind to CD75s-gangliosides with terminal Neu5Acα6Galβ4GlcNAc sequence. We, therefore, comparatively analyzed the content of CD75s-gangliosides and closely related iso-CD75s-gangliosides (terminated by Neu5Acα3Galβ4GlcNAc sequence) and the gene expression of associated β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) and β-galactoside α-2,3-sialyltransferase 6 (ST3GAL6), respectively, in 35 hepatocellular carcinoma (HCC) patients. Ganglioside structures were identified in lipid extracts of matched pairs of malignant and nonmalignant liver tissues by thin-layer chromatography immunodetection coupled with infrared matrix-assisted laser desorption/ionization orthogonal time-of-flight mass spectrometry. CD75s- and iso-CD75s-gangliosides were found to be deregulated in tumor tissues and showed an elevated occurrence in 35 and 41% of HCCs, respectively, compared with nontumoral liver tissues. Statistical analysis revealed a correlation between enhanced iso-CD75s-ganglioside amount and a poor histopathological differentiation (τ = 0.317, P = 0.045) and a significant association of CD75s- and iso-CD75s-ganglioside levels in nontumorous (τ = 0.392, P = 0.003) and in tumorous tissues (τ = 0.650, P < 0.001). Quantitative real-time polymerase chain reaction gene expression analysis of sialyltransferases exhibited no difference in ST6GAL1 expression in cancerous and adjacent noncancerous tissues. Interestingly, the ST3GAL6 expression was significantly diminished in HCCs (P = 0.003). The results indicate that the occurrence of CD75s- and iso-CD75s-gangliosides in tumor tissues is largely independent of the transcriptional expression of ST6GAL1 and ST3GAL6, respectively. Thus, further experiments are required to explore the rationale behind the differential ganglioside level and to validate the applicability of CD75s- and iso-CD75s-gangliosides as targets for individual HCC therapies.
唾液酸特异性细胞毒性凝集素 viscumin 及其重组等效物 rViscumin 特异性结合具有末端 Neu5Acα6Galβ4GlcNAc 序列的 CD75s-神经节苷脂。因此，我们比较分析了 35 例肝细胞癌 (HCC) 患者的 CD75s-神经节苷脂和密切相关的同工型 CD75s-神经节苷脂（末端为 Neu5Acα3Galβ4GlcNAc 序列）以及相关的 β-半乳糖苷 α-2,6-唾液酸转移酶 1 (ST6GAL1) 和 β-半乳糖苷 α-2,3-唾液酸转移酶 6 (ST3GAL6) 的基因表达。通过薄层层析免疫检测与红外基质辅助激光解吸/电离正交飞行时间质谱联用，在配对的恶性和非恶性肝组织的脂质提取物中鉴定了神经节苷脂结构。与非肿瘤性肝组织相比，肿瘤组织中 CD75s-和同工型 CD75s-神经节苷脂均失调，分别在 35%和 41%的 HCC 中升高。统计分析显示，增强的同工型 CD75s-神经节苷脂量与组织学分化不良呈正相关（τ=0.317，P=0.045），非肿瘤性（τ=0.392，P=0.003）和肿瘤组织（τ=0.650，P<0.001）中 CD75s-和同工型 CD75s-神经节苷脂水平之间存在显著相关性。唾液酸转移酶的实时定量聚合酶链反应基因表达分析显示，癌症和相邻非癌组织中 ST6GAL1 的表达无差异。有趣的是，HCC 中 ST3GAL6 的表达明显降低（P=0.003）。结果表明，肿瘤组织中 CD75s-和同工型 CD75s-神经节苷脂的发生在很大程度上独立于 ST6GAL1 和 ST3GAL6 的转录表达。因此，需要进一步的实验来探索差异神经节苷脂水平的原理，并验证 CD75s-和同工型 CD75s-神经节苷脂作为个体 HCC 治疗靶点的适用性。
