仓鼠博米尔斯基可移植黑色素瘤中的糖鞘脂

Glycosphingolipids in Bomirski transplantable melanomas in hamsters.

作者信息

Ren S L, Slominski A, Yu R K

机构信息

Department of Biochemistry and Molecular Biophysics, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0614.

出版信息

Cancer Res. 1989 Dec 15;49(24 Pt 1):7051-6.

PMID:2582447

Abstract

The glycosphingolipid compositions of Bomirski melanomas at different stages of differentiation, including Ab amelanotic melanoma (fast growing), Ma melanotic melanoma (slow growing), and MI hypomelanotic melanoma (slow growing), were studied. The total concentration of lipid-bound sialic acid in Ab amelanotic melanoma was found to be much lower than those in Ma and MI melanomas (0.8 micrograms versus 1.4 micrograms and 1.4 micrograms/mg of dry tissue, respectively). The ganglioside patterns in melanoma tissues were composed mainly of three components, which were confirmed as NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer (GM3), acetyl1-9-O-NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer (9-O-acetyl-GD3), and NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer(GD3) by structural analysis and monoclonal antibody detections. However, the relative ratios of these gangliosides expressed in the different types of melanomas were completely different. The MI melanoma tissues contained GM3 as the predominant species (greater than 90% of the total gangliosides) with very little of GD3 and 9-O-acetyl-GD3 gangliosides (less than 2% of the total gangliosides). In contrast, Ab amelanotic melanomas contained mainly 9-O-acetyl-GD3 (greater than 27%) and GD3 (greater than 51%) with lesser amounts of GM3. However, Ma melanoma had intermediate levels of GM3, GD3, and 9-O-acetyl GD3. The MI and Ma melanomas also contained monohexosylceramide (GL1) (about 60% as Gal beta 1-1'Cer and 40% as Glc beta 1-1'Cer in Ma and 30% as Gal beta 1-1'Cer and 70% as Glc beta 1-1'Cer in MI) and Gal beta 1-4Glc beta 1-1'Cer as the predominant neutral glycosphingolipid species. In contrast, Ab melanoma tissues contained more GalNAc beta 1-3GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-1'Cer (Gb5), Gal alpha 1-4Gal beta 1-4Glc beta 1-1'Cer (Gb3), and GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-1'Cer (Gb4) than MI and Ma melanomas. Our data suggest that the expression of glycosphingolipids in hamster melanoma cells may be closely related to cell growth and the degree of differentiation, with slow growing, highly differentiated cells expressing GM3 and GL1, and fast growing, undifferentiating cells having a preponderance of GD3, 9-O-acetyl-GD3, Gb5, Gb3, and Gb4.

摘要

研究了不同分化阶段的博米尔斯基黑色素瘤的糖鞘脂组成，包括无黑色素黑色素瘤（生长迅速）、黑色素黑色素瘤（生长缓慢）和低黑色素黑色素瘤（生长缓慢）。发现无黑色素黑色素瘤中脂质结合唾液酸的总浓度远低于黑色素黑色素瘤和低黑色素黑色素瘤（分别为0.8微克/毫克干组织，而黑色素黑色素瘤和低黑色素黑色素瘤为1.4微克/毫克干组织）。黑色素瘤组织中的神经节苷脂模式主要由三种成分组成，通过结构分析和单克隆抗体检测证实为NeuAcα2-3Galβ1-4Glcβ1-1'Cer（GM3）、乙酰基1-9-O-NeuAcα2-8NeuAcα2-3Galβ1-4Glcβ1-1'Cer（9-O-乙酰基-GD3）和NeuAcα2-8NeuAcα2-3Galβ1-4Glcβ1-1'Cer（GD3）。然而，这些神经节苷脂在不同类型黑色素瘤中的相对比例完全不同。低黑色素黑色素瘤组织中以GM3为主（占总神经节苷脂的90%以上），GD3和9-O-乙酰基-GD3神经节苷脂含量极少（占总神经节苷脂的不到2%）。相比之下，无黑色素黑色素瘤主要含有9-O-乙酰基-GD3（大于27%）和GD3（大于51%），GM3含量较少。然而，黑色素黑色素瘤中GM3、GD3和9-O-乙酰基-GD3的含量处于中间水平。低黑色素黑色素瘤和黑色素黑色素瘤还含有单己糖神经酰胺（GL1）（在黑色素黑色素瘤中约60%为Galβ1-1'Cer，40%为Glcβ1-1'Cer；在低黑色素黑色素瘤中30%为Galβ1-1'Cer，70%为Glcβ1-1'Cer），且Galβ1-4Glcβ1-1'Cer是主要的中性糖鞘脂种类。相比之下，无黑色素黑色素瘤组织中GalNAcβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-1'Cer（Gb5）、Galα1-4Galβ1-4Glcβ1-1'Cer（Gb3）和GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-1'Cer（Gb4）的含量比低黑色素黑色素瘤和黑色素黑色素瘤多。我们的数据表明，仓鼠黑色素瘤细胞中糖鞘脂的表达可能与细胞生长和分化程度密切相关，生长缓慢、高度分化的细胞表达GM3和GL1，而生长迅速、未分化的细胞中GD3、9-O-乙酰基-GD3、Gb5、Gb3和Gb4占优势。