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

Oncotarget. 2017 Apr 11;8(15):24902-24914. doi: 10.18632/oncotarget.15302.

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.

Keywords: GDNF; glioma cells; invasion; migration; precursor N-cadherin.

MeSH terms

  • Antigens, CD / metabolism*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cadherins / metabolism*
  • Cell Line, Tumor
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism*
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Matrix Metalloproteinase 9 / metabolism
  • Protein Precursors / metabolism
  • Transfection

Substances

  • Antigens, CD
  • CDH2 protein, human
  • Cadherins
  • GDNF protein, human
  • Glial Cell Line-Derived Neurotrophic Factor
  • Protein Precursors
  • MMP9 protein, human
  • Matrix Metalloproteinase 9