Reifenberger G, Bilzer T, Seitz R J, Wechsler W
Abteilungen für Neuropathologie, Universität Düsseldorf, Federal Republic of Germany.
Acta Neuropathol. 1989;78(3):270-82. doi: 10.1007/BF00687757.
The expression of glial fibrillary acidic protein (GFAP) and vimentin was investigated immunohistochemically in 104 experimental gliomas induced by transplancental application of ethylnitrosourea (ENU) in CDF rats. Immunoreactivity for vimentin was prominent in many astrocytic tumor cells and especially in small glioma cells forming anaplastic medulloblastoma-like foci in many tumors. The majority of tumor cells in oligodendroglial tumors were vimentin negative, except for some of the large polymorphous oligodendrogliomas which contained intermingled vimentin positive glioma cells. GFAP immunoreactivity was detectable only in a low fraction of tumor astrocytes and in a few exceptional cases some oligodendroglial tumor cells stained positive. Immunohistochemistry with antibodies against neurofilaments and cytokeratins revealed no staining in tumor cells of ENU-induced gliomas, while all oligodendrogliomatous tumors stained positive for HNK-1. Immunocytological and immunoblot investigations of the two rat glioma cell clones RG2 and F98, which are both derived from ENU-induced gliomas, showed a prominent expression of vimentin in monolayer cultures and in syngeneic intracerebral transplantation tumors. F98 additionally demonstrated a fraction of GFAP positive cells especially in confluent cultures and in intracerebral tumors. RG2, on the other hand, exhibited virtually no GFAP immunoreactivity in culture but showed individual GFAP positive tumor cells in intracerebral tumors. Our results revealed a more precise picture of the cellular differentiation in ENU-induced rat gliomas and in two widely used glioma cell lines. They underline the heterogeneity of experimental rat gliomas which may comprise cells at different stages of differentiation towards oligodendroglial or astroglial phenotype.
采用免疫组织化学方法,对经胎盘给予N-乙基-N-亚硝基脲(ENU)诱导产生的104例CDF大鼠实验性胶质瘤中胶质纤维酸性蛋白(GFAP)和波形蛋白的表达进行了研究。波形蛋白的免疫反应性在许多星形细胞瘤细胞中很明显,尤其是在许多肿瘤中形成间变性髓母细胞瘤样病灶的小胶质瘤细胞中。少突胶质细胞瘤中的大多数肿瘤细胞波形蛋白呈阴性,但一些大的多形性少突胶质细胞瘤中含有波形蛋白阳性的胶质瘤细胞。仅在一小部分肿瘤星形胶质细胞中可检测到GFAP免疫反应性,在少数特殊情况下,一些少突胶质细胞瘤细胞染色呈阳性。用抗神经丝和细胞角蛋白抗体进行免疫组织化学检测,结果显示ENU诱导的胶质瘤肿瘤细胞无染色,而所有少突胶质细胞瘤均呈HNK-1阳性染色。对两个均来源于ENU诱导的胶质瘤的大鼠胶质瘤细胞克隆RG2和F98进行免疫细胞化学和免疫印迹研究,结果显示在单层培养物和同基因脑内移植瘤中波形蛋白表达明显。F98还显示出一部分GFAP阳性细胞,尤其是在汇合培养物和脑内肿瘤中。另一方面,RG2在培养物中几乎没有GFAP免疫反应性,但在脑内肿瘤中显示出个别GFAP阳性肿瘤细胞。我们的结果揭示了ENU诱导的大鼠胶质瘤和两种广泛使用的胶质瘤细胞系中细胞分化的更精确情况。这些结果强调了实验性大鼠胶质瘤的异质性,其可能包含向少突胶质细胞或星形胶质细胞表型分化的不同阶段的细胞。