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与原发性脑肿瘤相关的神经节苷脂及其在源自这些肿瘤的细胞系中的表达。

Gangliosides associated with primary brain tumors and their expression in cell lines established from these tumors.

作者信息

Fredman P

机构信息

Department of Psychiatry and Neurochemistry, University of Göteborg, Sweden.

出版信息

Prog Brain Res. 1994;101:225-40. doi: 10.1016/s0079-6123(08)61952-4.

Abstract

Human primary brain tumors differ in their ganglioside composition when compared to adjacent tissues. One ganglioside found in all malignant glioma specimens, but not detected in normal adult brain, is 3'-isoLM1, a ganglioside of the lacto series. This ganglioside was also identified in medulloblastomas with astrocytic differentiation and in brain tissues containing benign proliferating astrocytes. The appearance of 3'-isoLM1 was seen over large regions of brain from glioma but was found mainly in areas either adjacent to the macroscopic tumor or areas corresponding to the tumor in the opposite hemisphere. A high concentration of 3'-isoLM1 was also seen in the corpus callosum, the anatomical structure along which glioma cells may migrate to the opposite brain hemisphere. Ganglioside expressed by cell lines established from primary malignant brain tumors varied widely among cell lines and within a given cell line propagated under different conditions. In in vitro-cultured glioma and medulloblastoma cell lines, gangliosides of the ganglio series dominated and the expression of the lacto series gangliosides, including 3'-isoLM1 was low if at all detectable. However, in vivo growth of solid subcutaneous tumors in nude mice or rats led to a significantly increased expression of the often dominant gangliosides of the lacto series and revealed a decreased expression of ganglio series gangliosides. In conclusion, these findings indicate that environmental factors could strongly influence the expression of gangliosides that may lead to a switch from the ganglio to the lacto series. These results also suggest that ganglioside 3'-isoLM1 is associated with proliferating astrocytes, of both neoplastic and non-neoplastic origin and that this ganglioside may be involved in cell-cell recognition and attachment during development and tumor cell migration.

摘要

与相邻组织相比,人类原发性脑肿瘤的神经节苷脂组成有所不同。在所有恶性胶质瘤标本中都能发现一种神经节苷脂,但在正常成人大脑中未检测到,它就是3'-异乳糖神经节苷脂1(3'-isoLM1),一种乳糖系列的神经节苷脂。在具有星形细胞分化的髓母细胞瘤以及含有良性增殖星形细胞的脑组织中也鉴定出了这种神经节苷脂。在胶质瘤患者大脑的大片区域都能看到3'-isoLM1的出现,但主要存在于与肉眼可见肿瘤相邻的区域或对侧半球对应肿瘤的区域。在胼胝体中也发现了高浓度的3'-isoLM1,胼胝体是胶质瘤细胞可能迁移到对侧脑半球的解剖结构。从原发性恶性脑肿瘤建立的细胞系所表达的神经节苷脂在不同细胞系之间以及在不同条件下传代培养的同一细胞系内差异很大。在体外培养的胶质瘤和髓母细胞瘤细胞系中,神经节系列的神经节苷脂占主导地位,而乳糖系列神经节苷脂(包括3'-isoLM1)的表达即使能检测到也很低。然而,在裸鼠或大鼠体内生长的实体皮下肿瘤会导致乳糖系列通常占主导的神经节苷脂表达显著增加,同时神经节系列神经节苷脂的表达减少。总之,这些发现表明环境因素可能强烈影响神经节苷脂的表达,从而导致从神经节系列向乳糖系列的转变。这些结果还表明,神经节苷脂3'-isoLM1与肿瘤性和非肿瘤性来源的增殖星形细胞相关,并且这种神经节苷脂可能参与发育过程中的细胞间识别和黏附以及肿瘤细胞迁移。

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