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黏蛋白-1在多发性骨髓瘤及其前体细胞中的表达:与糖基化和亚细胞定位的相关性

Expression of Mucin-1 in multiple myeloma and its precursors: correlation with glycosylation and subcellular localization.

作者信息

Andrulis Mindaugas, Ellert Elena, Mandel Ulla, Clausen Henrik, Lehners Nicola, Raab Marc-Steffen, Goldschmidt Hartmut, Schwartz-Albiez Reinhard

机构信息

Institute of Pathology, University of Heidelberg, Heidelberg, Germany.

出版信息

Histopathology. 2014 May;64(6):799-806. doi: 10.1111/his.12330. Epub 2014 Jan 21.

Abstract

AIMS

Recent reports suggest a possible role for extracellular (MUC1N) and transmembrane (MUC1C) subunits of Mucin 1 (MUC1) in the pathogenesis of multiple myeloma (MM). Nuclear translocation of MUC1C is involved in activation of various oncogenic signalling pathways and both MUC1 subunits are potential therapeutic targets. We aimed at performing a comprehensive expression analysis of the MUC1 subunits in plasma cell dyscrasias.

METHODS AND RESULTS

Immunohistochemistry with monoclonal antibodies against the MUC1N subunit (EMA and 5E10) tumour-associated glycoforms of MUC1N (5E5) and the MUC1C subunit were applied to a series of biopsies from normal controls (n = 10) and plasma cell dyscrasias (n = 121). Clonal plasma cells showed reduced MUC1N expression, and the 5E5 MUC1N epitope was expressed only in neoplastic plasma cells. Nuclear localization of MUC1C was equally frequent in all disease stages and did not differ from the control cases. Loss of both MUC1 subunits in MM (n = 12) was associated with significantly shorter overall survival and was more frequent in pretreated MM samples.

CONCLUSIONS

Our findings indicate that aberrant glycosylation of MUC1 is an early event in the pathogenesis of MM. In contrast, MUC1C nuclear localization is not likely to be a driver of tumour progression.

摘要

目的

近期报告表明,粘蛋白1(MUC1)的细胞外亚基(MUC1N)和跨膜亚基(MUC1C)在多发性骨髓瘤(MM)的发病机制中可能发挥作用。MUC1C的核转位参与多种致癌信号通路的激活,且这两个MUC1亚基均为潜在的治疗靶点。我们旨在对浆细胞异常增殖症中MUC1亚基进行全面的表达分析。

方法与结果

应用针对MUC1N亚基(上皮膜抗原和5E10)、MUC1N的肿瘤相关糖型(5E5)以及MUC1C亚基的单克隆抗体进行免疫组织化学检测,样本包括一系列来自正常对照(n = 10)和浆细胞异常增殖症(n = 121)的活检组织。克隆性浆细胞显示MUC1N表达降低,且5E5 MUC1N表位仅在肿瘤性浆细胞中表达。MUC1C的核定位在所有疾病阶段出现的频率相同,与对照病例无差异。MM患者(n = 12)中两个MUC1亚基的缺失与总生存期显著缩短相关,且在预处理的MM样本中更常见。

结论

我们的研究结果表明,MUC1的异常糖基化是MM发病机制中的早期事件。相比之下,MUC1C的核定位不太可能是肿瘤进展的驱动因素。

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