Wikstrand C J, He X M, Fuller G N, Bigner S H, Fredman P, Svennerholm L, Bigner D D
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
J Neuropathol Exp Neurol. 1991 Nov;50(6):756-69. doi: 10.1097/00005072-199111000-00007.
Monoclonal antibodies (MAb; DMAb, monoclonal antibodies derived at Duke Medical Center) directed against the oncofetally expressed lactotetraosyl gangliosides 3'-isoLM1 (IV3NeuAc-LcOse4Cer) and 3',6'-isoLD1 (IV3NeuAc,III6NeuAc-LcOse4Cer) were produced and their reactivity spectra compared to that of the alpha-3'-isoLM1 MAb SL-50. The IgM MAb SL-50 defines the epitope NeuAc (or NeuGc)alpha 2-3Gal beta 1-3GlcNAc, the terminal sequence of both gangliosides. SL-50 requires an unsubstituted GlcNAc residue; IgM DMAb-14 will accept the alpha 2-6 linked sialic acid to GlcNAc found in 3',6'-isoLD1. Immunohistochemical localization of 3'-isoLM1 was performed on 31 biopsy specimens of human gliomas; 15 (48%) expressed 3'-isoLM1 as defined by binding of MAb SL-50. Staining of small anaplastic cells, giant cells, and the glial component of gliosarcomas was observed. Neoplastic gemistocytes, when present, showed particularly intense staining. The 3'-isoLM1 and 3',6'-isoLD1 distribution in cultured cell lines and derived xenografts of primary tumors of the human central nervous system and of embryonal or neuroectodermal tumor derivation was determined. Six of 29 cell lines expressed 3'-isoLM1: 2/16 gliomas, 3/3 teratomas, 1/1 pancreatic adenocarcinoma. No cell line expressed detectable 3',6'-isoLD1 by immunostain analysis of ganglioside extracts. The 3'-iso-LM1-positive cell lines expressed it in xenograft form; in five xenografts, the corresponding cell lines of which were 3'-isoLM1-negative, it was a proportion of the monosialoganglioside fraction. 3',6'-isoLD1 was detected in two xenografts, D-54 MG (glioma) and PA-1 (teratoma). The demonstration of 3'-isoLM1 in gliomas in in vivo forms and the relatively infrequent expression by derived cultured cells suggest that ganglioside expression is modified by environmental forces. Expression of 3'-isoLM1 and 3',6'-isoLD1 in fetal and neonatal brain, in intense reactive astrocytosis such as polyunsaturated fatty acid lipidosis, and in primary neoplasms of the central nervous system suggests their role in cell-cell attachment during development, migration, and neoplastic transformation.
制备了针对癌胚表达的乳糖四糖神经节苷脂3'-异LM1（IV3NeuAc-LcOse4Cer）和3',6'-异LD1（IV3NeuAc,III6NeuAc-LcOse4Cer）的单克隆抗体（MAb；DMAb，在杜克医学中心获得的单克隆抗体），并将它们的反应谱与α-3'-异LM1单克隆抗体SL-50的反应谱进行了比较。IgM单克隆抗体SL-50定义了表位NeuAc（或NeuGc）α2-3Galβ1-3GlcNAc，这是两种神经节苷脂的末端序列。SL-50需要一个未取代的GlcNAc残基；IgM DMAb-14能识别3',6'-异LD1中GlcNAc上α2-6连接的唾液酸。对31例人脑胶质瘤活检标本进行了3'-异LM1的免疫组织化学定位；15例（48%）通过MAb SL-50的结合确定表达3'-异LM1。观察到小的间变性细胞、巨细胞以及胶质肉瘤的胶质成分有染色。当存在肿瘤性肥胖细胞时，显示出特别强烈的染色。测定了3'-异LM1和3',6'-异LD1在人中枢神经系统原发性肿瘤以及胚胎性或神经外胚层肿瘤来源的培养细胞系及其衍生异种移植物中的分布。29个细胞系中有6个表达3'-异LM1：2/16例胶质瘤、3/3例畸胎瘤、1/1例胰腺腺癌。通过对神经节苷脂提取物的免疫染色分析，没有细胞系表达可检测到的3',6'-异LD1。3'-异LM1阳性细胞系以异种移植物形式表达它；在5个异种移植物中，其相应的细胞系为3'-异LM1阴性，它是单唾液酸神经节苷脂部分的一部分。在两个异种移植物D-54 MG（胶质瘤）和PA-1（畸胎瘤）中检测到3',6'-异LD1。胶质瘤中3'-异LM1的体内形式的证实以及其衍生培养细胞中相对较少的表达表明神经节苷脂的表达受到环境因素的影响。3'-异LM1和3',6'-异LD1在胎儿和新生儿脑、强烈反应性星形细胞增生如多不饱和脂肪酸脂质沉积症以及中枢神经系统原发性肿瘤中的表达表明它们在发育、迁移和肿瘤转化过程中的细胞间附着中起作用。
