Differential expression of Hela-type caldesmon in tumour neovascularization: a new marker of angiogenic endothelial cells
Differential expression of Hela-type caldesmon in tumour neovascularization: a new marker of angiogenic endothelial cells
复制标题
DOI：
10.1002/path.1700
复制
发表时间：
2005-02-01
影响因子：
7.3
通讯作者：
Kros, JM
中科院分区：
文献类型：
--
作者：
Zheng, PP;van der Weiden, M;Kros, JM
Caldesmon (CaD) 是在多种细胞类型中发现的主要肌动球蛋白结合蛋白。选择性剪接产生至少两种高分子量异构体（h-CaD）和四种低分子量异构体（l-CaD）。 l-CaD 类的选择性剪接变体通过包含（Hela l-CaD）或排除（外显子 1 的 WI-38 l-CaD）进一步区分。目前，对于肿瘤新生血管形成中 Hela l-CaD 的差异表达一无所知。在先前的研究中，在神经胶质瘤血管中发现了 Hela 型转录本的表达，但在正常脑血管系统中没有发现。为了研究差异表达的转录本是否被翻译成蛋白质，最初，为了进一步确定这些发现是否适用于多种其他肿瘤类型的新血管形成，我们对来自不同器官（包括乳腺癌、肺癌、肾、结肠、胃、卵巢、子宫、前列腺、甲状腺、肝脏）的大量癌症进行了检测，总共 180 例病例。 Hela l-CaD 在肿瘤新生血管形成的早期优先表达，并且 Hela l-CaD+ 内皮细胞 (EC) 经常增大、多核，并出现细长的细胞突起或游离的细胞质碎片，与运动细胞的特征相关，在 Hela l-CaD+ EC 中观察到粘着斑解体和足小体样结构的形成。因此，研究结果支持这样的观点，即静止的 EC 会发生运动激活，这是普遍存在的肿瘤相关新生血管形成所必需的。数据表明，Hela l-CaD 可被视为肿瘤新生血管形成早期阶段的血管生成 EC 的标志物。版权所有 (C) 2005 英国和爱尔兰病理学会，John Wiley Sons, Ltd 出版。
Caldesmon (CaD) is a major actomyosin-binding protein found in various cell types. There are at least two high-molecular-weight isoforms (h-CaD) and four low-molecular-weight isoforms (l-CaD) produced by alternative splicing. The alternatively spliced variants of the l-CaD class are further differentiated by inclusion (Hela l-CaD) or exclusion (WI- 38 l-CaD of exon 1. Currently, nothing is known about differential expression of the Hela l-CaD in tumour neovascularization. In a previous study, expression of the Hela-type transcripts was found in glioma blood vessels but not in the normal cerebral vasculature. To investigate whether the differentially expressed transcripts are translated into protein, a specific antibody against the peptide encoded by exon 1 was raised. Initially, exclusive expression of the protein in glioma vasculature was confirmed. To determine further whether these findings are generalizable to neovascularization in a wide variety of other tumour types, a large cohort of cancers derived from various organs, including breast, lung, kidney, colon, stomach, ovary, uterus, prostate, thyroid, liver, giving a total of 180 cases, were examined. Expression of the Hela l-CaD was restricted to tumour vasculature and was not found in normal blood vessels. Hela l-CaD was preferentially expressed in the early stage of tumour neovascularization and the Hela l-CaD+ endothelial cells (ECs) were frequently enlarged, multinucleated, and developed elongated cell projections or free fragments of cytoplasm, correlating with the features of motile cells. In the Hela l-CaD+ ECs, disassembly of focal adhesion and the formation of podosome-like structures was observed. Therefore, the findings support the notion that quiescent ECs undergo activation of motility, necessary for ubiquitous tumour-associated neovascularization. The data indicate that Hela l-CaD can be considered as a marker for angiogenic ECs during the early stages of tumour neovascularization. Copyright (C) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.