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由小鼠单克隆抗体定义的黑色素瘤和黑色素细胞的表面抗原:培养细胞和组织中抗原表达的特异性分析与比较

Surface antigens of melanomas and melanocytes defined by mouse monoclonal antibodies: specificity analysis and comparison of antigen expression in cultured cells and tissues.

作者信息

Real F X, Houghton A N, Albino A P, Cordon-Cardo C, Melamed M R, Oettgen H F, Old L J

出版信息

Cancer Res. 1985 Sep;45(9):4401-11.

PMID:4028024
Abstract

Mouse monoclonal antibodies (mAb) detecting 13 distinct systems of surface antigens on cultured melanocytes and melanomas were tested for reactivity with panels of (a) normal and malignant cultured cells; (b) normal adult and fetal tissues; and (c) specimens of metastatic melanoma and other tumor types. The objectives of this study were to compare antigen expression in cultured versus noncultured cells, to develop a panel of mAbs that identify subsets of melanomas, and to provide requisite information about antibody specificity in preparation for the use of antibodies in the diagnosis, imaging, and therapy of melanoma. Five of the melanoma surface antigens have been well characterized biochemically [GD3, chondroitin sulfate proteoglycan, HLA Class II antigens, glycoprotein of molecular weight 130,000 (gp130), and glycoprotein Mr 95,000/protein Mr 97,000 (gp95/p97)]. Three antigens have been related to melanocyte differentiation (HLA Class II, M111/M231, and M144), and six provide additional markers for subsets of cultured melanomas. mAb R24 reacts with the disialoganglioside GD3, a predominant ganglioside on cultured melanoma cells and other cells of neuroectodermal origin. A high proportion of melanoma, astrocytoma, and sarcoma tissue specimens were GD3+. In normal tissues, reactivity of mAb R24 was restricted to melanocytes, neuronal and glial cells in the central nervous system, parotid gland, adrenal medullary cells, and rare cells in the connective tissue. mAb B5 detects a chondroitin sulfate proteoglycan that is expressed by most melanoma and astrocytoma cell lines and by cultured melanocytes. Most of the melanoma and astrocytoma specimens were B5+, whereas other tumor types tested were B5-. mAb 13-17, which detects a monomorphic determinant of HLA Class II antigens, reacted with melanomas, and with a variety of other cancers, but not with normal skin melanocytes. There is considerable variability in the expression of GD3 and HLA Class II antigens in individual melanoma specimens; cotyping for these two antigens showed no evidence for coordinate expression. mAb L101 detects gp130 and mAb L235 detects gp95, antigens that are strongly expressed on a broad range of cultured cell types. In contrast to their wide distribution on cultured cells, gp130 expression in tissues was generally restricted to a subset of melanomas and some normal cells, and gp95 was detected on only a small number of melanomas. mAb M111/mAb M231 and mAb M144 define intermediate and late stage differentiation markers of cultured melanocytes and melanomas.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

检测培养的黑素细胞和黑色素瘤表面抗原13个不同系统的小鼠单克隆抗体(mAb),针对以下几类细胞进行了反应性测试:(a)正常和恶性培养细胞;(b)正常成人和胎儿组织;(c)转移性黑色素瘤和其他肿瘤类型的标本。本研究的目的是比较培养细胞与未培养细胞中的抗原表达,开发一组可识别黑色素瘤亚群的单克隆抗体,并提供关于抗体特异性的必要信息,为在黑色素瘤的诊断、成像和治疗中使用抗体做准备。其中5种黑色素瘤表面抗原已在生化方面得到充分表征[GD3、硫酸软骨素蛋白聚糖、HLA II类抗原、分子量为130,000的糖蛋白(gp130)以及分子量95,000/蛋白分子量97,000的糖蛋白(gp95/p97)]。3种抗原与黑素细胞分化相关(HLA II类、M111/M231和M144),另外6种为培养的黑色素瘤亚群提供了额外的标志物。单克隆抗体R24与双唾液酸神经节苷脂GD3反应,GD3是培养的黑色素瘤细胞和其他神经外胚层来源细胞上的主要神经节苷脂。高比例的黑色素瘤、星形细胞瘤和肉瘤组织标本为GD3阳性。在正常组织中,单克隆抗体R24的反应性仅限于黑素细胞、中枢神经系统的神经元和神经胶质细胞、腮腺、肾上腺髓质细胞以及结缔组织中的罕见细胞。单克隆抗体B5检测到一种硫酸软骨素蛋白聚糖,大多数黑色素瘤和星形细胞瘤细胞系以及培养的黑素细胞都表达该蛋白聚糖。大多数黑色素瘤和星形细胞瘤标本为B5阳性,而测试的其他肿瘤类型为B5阴性。检测HLA II类抗原单态决定簇的单克隆抗体13 - 17与黑色素瘤以及多种其他癌症反应,但不与正常皮肤黑素细胞反应。在个体黑色素瘤标本中,GD3和HLA II类抗原的表达存在相当大的变异性;对这两种抗原进行共分型未发现协同表达的证据。单克隆抗体L101检测gp130,单克隆抗体L235检测gp95,这些抗原在广泛的培养细胞类型上强烈表达。与它们在培养细胞上的广泛分布不同,gp130在组织中的表达通常仅限于一部分黑色素瘤和一些正常细胞,而仅在少数黑色素瘤中检测到gp95。单克隆抗体M111/单克隆抗体M231和单克隆抗体M144定义了培养的黑素细胞和黑色素瘤的中期和晚期分化标志物。(摘要截短于400字)

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