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超越血管:非内皮细胞中含血管内皮(VE)-钙黏蛋白连接的出现及区域聚集

Beyond vessels: occurrence and regional clustering of vascular endothelial (VE-)cadherin-containing junctions in non-endothelial cells.

作者信息

Boda-Heggemann Judit, Régnier-Vigouroux Anne, Franke Werner W

机构信息

Helmholtz Group for Cell Biology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.

出版信息

Cell Tissue Res. 2009 Jan;335(1):49-65. doi: 10.1007/s00441-008-0718-1. Epub 2008 Nov 11.

Abstract

The genes encoding transmembrane glycoproteins of the cadherin family, i.e., the Ca(2+)-dependent cell-cell adhesion molecules, are typically expressed in cell-type- or cell-lineage-specific patterns. One of them, vascular endothelial (VE)-cadherin, is widely considered to be specific for vascular endothelia in which it is either the sole or the predominant cadherin, often co-existing with N-cadherin. This specificity of VE-cadherin for vascular endothelial cells is important not only in blood and lymph vessel biology and medicine, but also for cell-type-based diagnoses, notably those of metastatic tumors. Surprisingly, however, we have recently noted the frequent synthesis, surface exposure, and junction assembly of VE-cadherin in certain other cells, in which this glycoprotein is clustered into adherens junctions (AJs), either alone or in combination with N-cadherin and/or cadherin-11. Such cells include mammalian astrocytes and glioma, probably mostly astrocytoma cells growing in culture, and a specific subtype of astrocytoma in situ. Moreover, VE-cadherin synthesis and AJ assembly, plus the regional clustering of such AJs in certain domains, are not clonally fixed but can appear again and again in cells of the progeny of cloned homogeneous-appearing individual cells, thus resulting in clonal cell colonies that are often heterogeneous in their cadherin junction patterns. We discuss the constitutive presence of VE-cadherin in some non-endothelial cells with respect to certain architectural features and possible physiological and pathogenic functions of the cells, and in comparison with recent reports of VE-cadherin-positive melanomas.

摘要

编码钙黏蛋白家族跨膜糖蛋白的基因,即依赖钙离子的细胞间黏附分子,通常以细胞类型或细胞谱系特异性模式表达。其中之一,血管内皮(VE)钙黏蛋白,被广泛认为是血管内皮细胞所特有的,在血管内皮细胞中它要么是唯一的钙黏蛋白,要么是主要的钙黏蛋白,常与N钙黏蛋白共存。VE钙黏蛋白对血管内皮细胞的这种特异性不仅在血管和淋巴管生物学及医学中很重要,而且对于基于细胞类型的诊断,尤其是转移性肿瘤的诊断也很重要。然而,令人惊讶的是,我们最近注意到在某些其他细胞中频繁合成、表面暴露和连接组装VE钙黏蛋白,在这些细胞中这种糖蛋白聚集形成黏着连接(AJs),要么单独存在,要么与N钙黏蛋白和/或钙黏蛋白-11结合存在。这类细胞包括哺乳动物星形胶质细胞和胶质瘤,可能主要是培养中的星形细胞瘤细胞,以及原位星形细胞瘤的一种特定亚型。此外,VE钙黏蛋白的合成和AJ组装,以及此类AJs在某些区域的聚集,并非克隆固定的,而是可以在克隆的外观均一的单个细胞后代的细胞中反复出现,从而导致其钙黏蛋白连接模式往往异质性的克隆细胞集落。我们讨论了VE钙黏蛋白在一些非内皮细胞中的组成性存在与这些细胞的某些结构特征、可能的生理和致病功能的关系,并与最近关于VE钙黏蛋白阳性黑色素瘤的报道进行了比较。

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