Cdh4 down-regulation impairs in vivo infiltration and malignancy in patients derived glioblastoma cells

Davide Ceresa, Francesco Alessandrini, Lorenzo Bosio, Daniela Marubbi, Daniele Reverberi, Paolo Malatesta, Irene Appolloni

Research output: Contribution to journalArticle

Abstract

The high invasive phenotype of glioblastoma is one of the main causes of therapy inefficacy and tumor relapse. Cell adhesion molecules of the cadherin family are involved in cell migration and are known as master regulators of epithelial tumor invasiveness, but their role in glioblastoma is less understood. In particular, we recently demonstrated, in the syngeneic murine model, the occurrence of a previously undescribed cadherin switch between Cdh2 and Cdh4 during gliomagenesis, which is necessary for the acquisition of the highly infiltrative and tumorigenic phenotype of these cells. In the present study, we tested the role of Cdh4 in human gliomas. Our results on patient-derived glioma cells demonstrate a positive correlation between Cdh4 expression levels and the loss of cell–cell contact inhibition of proliferation controls that allows cells to proliferate over confluence. Moreover, the silencing of Cdh4 by artificial microRNAs induced a decrease in the infiltrative ability of human glioma cells both in vitro and in vivo. More strikingly, Cdh4 silencing induced an impairment of the tumorigenic potential of these cells after orthotopic transplantation in immunodeficient mice. Overall, we conclude that in human glioblastoma, Cdh4 can also actively contribute in regulating cell invasiveness and malignancy.

Original languageEnglish
Article number4028
JournalInternational Journal of Molecular Sciences
Volume20
Issue number16
DOIs
Publication statusPublished - Aug 2 2019

Keywords

  • Adherent junctions
  • Brain tumor
  • Cell polarity
  • Contact inhibition
  • Migration
  • Proliferation
  • R-cadherin

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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