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Tenascin-C is expressed by human glioma in vivo and shows a strong association with tumor blood vessels

机译:Tenascin-C在体内由人神经胶质瘤表达,并与肿瘤血管密切相关

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The extracellular matrix (ECM) protein tenascin-C (TN-C) is upregulated within glioma tissues and cultured glioma cell lines. TN-C possesses a multi-modular structure and a variety of functional properties have been reported for its domains. We describe five novel monoclonal antibodies identifying different domains of TN-C. The epitopes for these antibodies were investigated by using recombinantly expressed fibronectin type III domains of TN-C. The biological effects of TN-C fragments on glioma cell proliferation and adhesion were analyzed. The expression pattern of TN-C in human glioma tissue sections and in glioma cell lines was studied with the novel library of monoclonal antibodies. The immunocytochemical analyses of the established human glioma cell lines U-251-MG, U-373-MG and U-87-MG revealed distinct staining patterns for each antibody. Robust expression of TN-C was found within the tumor mass of surgery specimens from glioblastoma. In many cases, the expression of this ECM molecule was clearly associated with blood vessels, particularly with microvessels. Three of the new antibodies highlighted individual TN-C-expressing single cells in glioma tissues. The effect of TN-C domains on glioma cells was examined by a BrdU-proliferation assay and an adhesion assay. Short fragments of constitutively expressed TN-C-domains did not exert significant effects on the proliferation of glioma cells, whereas the intact molecule increased cell division rates. In contrast, the long fragment TNfnALL containing all of the FNIII domains of TN-C decreased proliferation. Additionally, we found strong differences between the adhesion-influencing properties of the recombinant fragments on glioma cells.
机译:细胞外基质(ECM)蛋白腱生蛋白C(TN-C)在神经胶质瘤组织和培养的神经胶质瘤细胞系中上调。 TN-C具有多模块结构,其结构域已报道了多种功能特性。我们描述了五种鉴定TN-C不同域的新型单克隆抗体。通过使用TN-C的重组表达的纤连蛋白III型结构域研究了这些抗体的表位。分析了TN-C片段对神经胶质瘤细胞增殖和粘附的生物学效应。用新型单克隆抗体文库研究了TN-C在人神经胶质瘤组织切片和神经胶质瘤细胞系中的表达模式。建立的人神经胶质瘤细胞系U-251-MG,U-373-MG和U-87-MG的免疫细胞化学分析揭示了每种抗体的独特染色模式。在胶质母细胞瘤的手术标本的肿瘤块中发现了TN-C的强表达。在许多情况下,这种ECM分子的表达显然与血管有关,特别是与微血管有关。其中三种新抗体突出了神经胶质瘤组织中表达TN-C的单个细胞。 TN-C结构域对神经胶质瘤细胞的作用通过BrdU-增殖测定法和粘附测定法检查。组成性表达的TN-C结构域的短片段对胶质瘤细胞的增殖没有显着影响,而完整分子则增加了细胞分裂率。相反,含有所有TN-C FNIII结构域的长片段TNfnALL降低了增殖。此外,我们发现神经胶质瘤细胞中重组片段的粘附影响特性之间的强烈差异。

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