Precursor N-cadherin mediates glial cell line-derived neurotrophic factor-promoted human malignant glioma

Abstract

// Ye Xiong 1, * , Liyun Liu 1, * , Shuang Zhu 1 , Baole Zhang 1 , Yuxia Qin 1 , Ruiqin Yao 1 , Hao Zhou 2 , Dian Shuai Gao 1 1 Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China 2 Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Food and Environmental, Dalian University of Technology, Panjin Campus, Panjin 124221, China * These authors have contributed equally to this work Correspondence to: Dian Shuai Gao, email: gds@xzhmu.edu.cn Keywords: precursor N-cadherin, glioma cells, GDNF, migration, invasion Received: July 20, 2016     Accepted: January 19, 2017     Published: February 12, 2017 ABSTRACT 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.