Bernstein J J, Anagnostopoulos A V, Hattwick E A, Laws E R
Department of Neurological Surgery, George Washington University School of Medicine, Washington, D.C.
J Neurosurg. 1993 Feb;78(2):240-51. doi: 10.3171/jns.1993.78.2.0240.
Overexpression of human-specific c-neu proto-oncogene transmembrane tyrosine kinase receptor protein (p185) is an index of cell transformation and of poor patient survival in several malignancies. The authors studied this protein in low- and high-grade human malignant astrocytomas before and after xenografting into aspiration pockets in rat cortex. Human-specific p185c-neu-positive cells were found in tumor specimens from all grades of astrocytoma. Significantly fewer p185c-neu-positive cells were observed in the low-grade versus the high-grade astrocytomas examined (p < 0.05). Human specific p185c-neu-positive cells were also positive for the human major histocompatibility complex, human leukocyte antigen (HLA)-DR, as well as glial fibrillary acidic protein and S-100 protein. Fresh suspensions of tumor tissue were prelabeled with the plant lectin Phaseolus vulgaris leukoagglutinin and xenografted into pockets in rat cortex. A class of human p185c-neu-positive cells found in tissue samples from all grades of astrocytoma migrated in the rat brain along parallel and intersecting nerve fibre bundles and basement membrane-lined surfaces. Migrated p185c-neu-positive cells were also positive for HLA-DR, Phaseolus vulgaris leukoagglutinin, glial fibrillary acidic protein, and S-100 protein, suggesting that they were in fact human astrocytoma cells. Simultaneous expression of human p185c-neu, HLA-DR, and glial fibrillary acidic protein was observed in a class of human malignant astrocytoma cells in both tumor tissue and xenografted cells that migrated into rat brain. These molecules are signature proteins for the study of the spread of human malignant astrocytomas in an animal model, and indicate that transformed human malignant astrocytoma cells can migrate within the parenchyma of the central nervous system and could play a role in the development of multifocal tumors.
人类特异性c-neu原癌基因跨膜酪氨酸激酶受体蛋白（p185）的过表达是几种恶性肿瘤中细胞转化和患者预后不良的一个指标。作者在将人类恶性星形细胞瘤低级别和高级别样本异种移植到大鼠皮质的抽吸腔前后，对该蛋白进行了研究。在所有级别的星形细胞瘤肿瘤标本中均发现了人类特异性p185c-neu阳性细胞。在所检查的低级别星形细胞瘤中观察到的p185c-neu阳性细胞明显少于高级别星形细胞瘤（p<0.05）。人类特异性p185c-neu阳性细胞对人类主要组织相容性复合体、人类白细胞抗原（HLA）-DR以及胶质纤维酸性蛋白和S-100蛋白也呈阳性。肿瘤组织的新鲜悬液先用植物凝集素菜豆白细胞凝集素预标记，然后异种移植到大鼠皮质的腔中。在所有级别的星形细胞瘤组织样本中发现的一类人类p185c-neu阳性细胞在大鼠脑中沿着平行和交叉的神经纤维束以及基底膜衬里表面迁移。迁移的p185c-neu阳性细胞对HLA-DR、菜豆白细胞凝集素、胶质纤维酸性蛋白和S-100蛋白也呈阳性，表明它们实际上是人类星形细胞瘤细胞。在肿瘤组织和迁移到大鼠脑中的异种移植细胞中的一类人类恶性星形细胞瘤细胞中观察到人类p185c-neu、HLA-DR和胶质纤维酸性蛋白的同时表达。这些分子是研究人类恶性星形细胞瘤在动物模型中扩散的标志性蛋白，并表明转化的人类恶性星形细胞瘤细胞可在中枢神经系统实质内迁移，并可能在多灶性肿瘤的发生中起作用。
