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单克隆抗体GB24所识别的抗原在人乳腺癌上的高表达:恶性肿瘤细胞对抗补体攻击的一种预防机制?

High expression of the antigen recognized by the monoclonal antibody GB24 on human breast carcinomas: a preventive mechanism of malignant tumor cells against complement attack?

作者信息

Hofman P, Hsi B L, Manie S, Fenichel P, Thyss A, Rossi B

机构信息

INSERM U364, University of Nice, France.

出版信息

Breast Cancer Res Treat. 1994;32(2):213-9. doi: 10.1007/BF00665772.

DOI:10.1007/BF00665772
PMID:7532466
Abstract

GB24 is a mouse monoclonal antibody raised against a common trophoblast-lymphocyte cross-reactive antigen. GB24 detects the membrane cofactor protein (MCP, CD46), a member of the complement regulatory protein family, which serves as a cofactor for factor 1 mediated cleavage of C3b. This study investigated the reactivity of GB24 on 38 breast carcinomas and 34 normal/benign breast tissues by immunochemistry as well as the reactivity of F2B7-2, an antibody specific to the decay accelerating factor (DAF, CD55) of the complement. GB24 staining was present on both normal tissue and benign lesions, but very strong diffuse reactivity was observed on carcinomas. This reactivity increased with the tumor grade. By contrast, malignant tumor cells lacked DAF expression. F2B7-2 antibody reacted weakly with benign epithelial cells. Results were studied by computer assisted image analysis to accurately define the mean optical densities. The densitometric analysis of MCP positive carcinomas showed a high intensity of the staining. Expression of MCP and DAF on MCF-7 cell lines was analyzed by flow cytometry. MCF-7 cell lines were strongly stained by mAb GB24 only. These data suggest that selectively enhanced expression of the antigen recognized by GB24 is associated with malignant breast disorders. This high expression, which may reflect a protective mechanism by which tumor cells survive complement activation, may prove useful as a marker of malignant transformation.

摘要

GB24是一种针对常见的滋养层-淋巴细胞交叉反应抗原产生的小鼠单克隆抗体。GB24可检测膜辅因子蛋白(MCP,CD46),它是补体调节蛋白家族的一员,作为I因子介导的C3b裂解的辅因子。本研究通过免疫化学方法研究了GB24在38例乳腺癌和34例正常/良性乳腺组织中的反应性,以及补体衰变加速因子(DAF,CD55)特异性抗体F2B7-2的反应性。GB24染色在正常组织和良性病变中均有出现,但在癌组织中观察到非常强烈的弥漫性反应。这种反应性随肿瘤分级增加而增强。相比之下,恶性肿瘤细胞缺乏DAF表达。F2B7-2抗体与良性上皮细胞反应较弱。通过计算机辅助图像分析研究结果以准确确定平均光密度。对MCP阳性癌组织的光密度分析显示染色强度较高。通过流式细胞术分析MCF-7细胞系上MCP和DAF的表达。MCF-7细胞系仅被单克隆抗体GB24强烈染色。这些数据表明,GB24识别的抗原选择性增强表达与乳腺恶性疾病有关。这种高表达可能反映了肿瘤细胞在补体激活中存活的一种保护机制,可能作为恶性转化的一个标志物。

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Separation of self from non-self in the complement system.补体系统中自身与非自身的区分。
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Membrane cofactor protein of complement is present on human fibroblast, epithelial, and endothelial cells.补体膜辅因子蛋白存在于人类成纤维细胞、上皮细胞和内皮细胞上。
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Monoclonal antibody GB24 recognizes a trophoblast-lymphocyte cross-reactive antigen.
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Identification of the complement decay-accelerating factor (DAF) on epithelium and glandular cells and in body fluids.鉴定上皮细胞、腺细胞及体液中的补体衰变加速因子(DAF)。
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Complement-mediated tumor cell damage induced by antibodies against membrane cofactor protein (MCP, CD46).抗膜辅因子蛋白(MCP,CD46)抗体诱导的补体介导的肿瘤细胞损伤。
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