Precursor N-cadherin mediates glial cell line-derived neurotrophic factor-promoted human malignant glioma.
Precursor N-cadherin mediates glial cell line-derived neurotrophic factor-promoted human malignant glioma.
复制标题
前体 N-钙粘蛋白介导神经胶质细胞系衍生的神经营养因子促进的人恶性神经胶质瘤。
DOI：
10.18632/oncotarget.15302
复制
发表时间：
2017-04-11
期刊：
影响因子：
--
通讯作者：
Gao DS
中科院分区：
文献类型：
--
作者：
Xiong Y;Liu L;Zhu S;Zhang B;Qin Y;Yao R;Zhou H;Gao DS
作为最常见的原发性脑肿瘤，神经胶质瘤具有高度转移性、侵袭性，并且具有高水平的神经胶质细胞源性神经营养因子（GDNF）的特征。 GDNF是侵袭性胶质瘤细胞生长的重要因素；然而，所涉及的根本机制尚不清楚。在这项研究中，我们证实，与正常脑组织相比，大多数神经胶质瘤中 N-钙粘蛋白前体（N-钙粘蛋白原）的表达显着较高。我们的研究结果表明，GDNF 与 proN-cadherin 的细胞外结构域相互作用，这表明 proN-cadherin 介导 GDNF 诱导的胶质瘤细胞迁移和侵袭。我们假设proN-cadherin可能会导致邻近细胞内的同型粘附丧失，同时通过某种机制促进细胞外基质（ECM）内的异型粘附。这项研究还表明，GDNF 和 proN-cadherin 之间的相互作用会激活特定的细胞内信号通路；此外，GDNF 促进基质金属蛋白酶 9 (MMP-9) 的分泌，MMP-9 通过 proN-钙粘蛋白降解 ECM。为了实现开发神经胶质瘤新疗法的未来目标，这项研究揭示了神经胶质瘤细胞迁移和侵袭的独特机制。
As the most prevalent primary brain tumor, gliomas are highly metastatic, invasive and are characteristic of high levels of glial cell-line derived neurotrophic factor (GDNF). GDNF is an important factor for invasive glioma cell growth; however, the underlying mechanism involved is unclear. In this study, we affirm a significantly higher expression of the precursor of N-cadherin (proN-cadherin) in most gliomas compared with normal brain tissues. Our findings reveal that GDNF interacts with the extracellular domain of proN-cadherin, which suggests that proN-cadherin mediates GDNF-induced glioma cell migration and invasion. We hypothesize that proN-cadherin might cause homotypic adhesion loss within neighboring cells and at the same time promote heterotypic adhesion within the extracellular matrix (ECM) through a certain mechanism. This study also demonstrates that the interaction between GDNF and proN-cadherin activates specific intracellular signaling pathways; furthermore, GDNF promoted the secretion of matrix metalloproteinase-9 (MMP-9), which degrades the ECM via proN-cadherin. To reach the future goal of developing novel therapies of glioma, this study, reveals a unique mechanism of glioma cell migration and invasion.