Asano Kenichiro, Duntsch Christopher D, Zhou Qihong, Weimar James D, Bordelon Dwight, Robertson Jon H, Pourmotabbed Tayebeh
Department of Neurosurgery, The University of Tennessee Health Science Center, Memphis, TN, USA.
J Neurooncol. 2004 Oct;70(1):3-15. doi: 10.1023/b:neon.0000040811.14908.f2.
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, up-regulation 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 up-regulation 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.
钙黏蛋白是依赖钙离子的细胞黏附分子，在多细胞生物的组织构建和形态发生中发挥重要作用。在过去几年里，文献中出现了关于钙黏蛋白参与肿瘤侵袭和转移的报道。钙黏蛋白通常根据组织的生物学需求呈现上调和下调。此外，N-钙黏蛋白的上调被认为在肿瘤发展早期的肿瘤形成中很重要。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-钙黏蛋白，发现与正常脑组织相比，N-钙黏蛋白mRNA表达上调。为了研究N-钙黏蛋白表达对体外和体内侵袭与转移的影响，我们在通常N-钙黏蛋白水平较低的大鼠C6胶质瘤细胞系中过表达了N-钙黏蛋白。我们发现N-钙黏蛋白的上调导致对IV型胶原、纤连蛋白和层粘连蛋白的黏附略有下降，但对I型胶原的黏附在统计学上有显著下降。此外，在细胞外基质侵袭试验中，N-钙黏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-钙黏蛋白表达与向周围组织的侵袭、边缘不规则和颅外侵袭呈负相关。总之，这些数据共同表明N-钙黏蛋白水平在胶质瘤的恶性行为中很重要，并且可能作为高级别胶质瘤患者的预后指标。
