Correlation of N-cadherin expression in high grade gliomas with tissue invasion
Correlation of N-cadherin expression in high grade gliomas with tissue invasion
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DOI：
10.1023/b:neon.0000040811.14908.f2
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发表时间：
2004-10-01
影响因子：
3.9
通讯作者：
Pourmotabbed, T
中科院分区：
文献类型：
--
作者：
Asano, K;Duntsch, CD;Pourmotabbed, T
钙粘蛋白是一种钙离子依赖的细胞粘附分子，在多细胞生物的组织构建和形态发生中起着重要作用。在过去的几年中，文献中出现了描述钙粘蛋白参与肿瘤侵袭和转移的报道。钙粘蛋白通常根据组织的生物学需要表现出上调和下调。此外，N-钙粘蛋白的上调被认为对肿瘤发展早期阶段的肿瘤形成很重要。我们通过微阵列分析研究了原发性胶质母细胞瘤患者手术标本中的N-钙粘蛋白，发现与正常脑相比，N-钙粘蛋白mRNA表达上调。为了研究N-cadherin表达对体外和体内侵袭和转移的影响，我们在通常具有低水平N-cadherin的大鼠C6胶质瘤细胞系中过表达N-cadherin。我们发现N-钙粘蛋白的上调导致与IV型胶原、纤连蛋白和层粘连蛋白的粘附性轻微降低，但与I型胶原的粘附性在统计学上显著降低。此外，在细胞外基质侵袭试验中，N-钙粘蛋白表达的增加与侵袭行为的显著降低相关。然后，我们在大鼠颅内胶质瘤模型中对这些细胞系进行了体内研究，发现N-cadherin表达与周围组织的浸润、不规则边缘和颅外浸润呈负相关。总之，这些数据共同表明，N-钙粘蛋白水平在胶质瘤的恶性行为中是重要的，并可作为高级别胶质瘤患者的预后指标。
Cadherins are Ca2+-dependent cell adhesion molecules that play an important role in tissue construction and morphogenesis in multicellular organisms. Over the last few years, reports have emerged in the literature describing the involvement of cadherins in tumor invasion and metastasis. Cadherins typically demonstrate up and down-regulation according to the biological needs of the tissue. Additionally, upregulation of N-cadherin is thought to be important for tumor formation in early stages of tumor development. We studied N-cadherin in surgical specimens of patients with primary glioblastoma by microarray analysis and found that N-cadherin mRNA expression is up-regulated compared to normal brain. To study the effects of N-cadherin expression on invasion and metastasis in vitro and in vivo, we overexpressed N-cadherin in the rat C6 glioma cell line which normally has low levels of N-cadherin. We found that upregulation of N-cadherin resulted in a slight decreased adhesion to type IV collagen, fibronectin, and laminin, but statistically significant decreased adhesion to type I collagen. Furthermore, increased expression of N-cadherin correlated with a dramatic decrease in invasive behavior in extracellular matrix invasion assays. We then proceeded to study these cell lines in vivo in a rat intracranial glioma model, and found that N-cadherin expression inversely correlated with invasion into surrounding tissues, irregular margins, and extracranial invasion. In summary, these data collectively demonstrate that N-cadherin levels are important in the malignant behavior of gliomas, and may serve as a prognostic indicator for patients with high-grade gliomas.