Glioma cell dispersion is driven by α5 integrin-mediated cell-matrix and cell-cell interactions

Anne Florence Blandin, Fanny Noulet, Guillaume Renner, Marie Cécile Mercier, Laurence Choulier, Romain Vauchelles, Philippe Ronde, Franck Carreiras, Nelly Etienne-Selloum, Gyorgy Vereb, Isabelle Lelong-Rebel, Sophie Martin, Monique Dontenwill, Maxime Lehmann

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Glioblastoma multiform (GBM) is the most common and most aggressive primary brain tumor. The fibronectin receptor, α5 integrin is a pertinent novel therapeutic target. Despite numerous data showing that α5 integrin support tumor cell migration and invasion, it has been reported that α5 integrin can also limit cell dispersion by increasing cell-cell interaction. In this study, we showed that α5 integrin was involved in cell-cell interaction and gliomasphere formation. α5-mediated cell-cell cohesion limited cell dispersion from spheroids in fibronectin-poor microenvironment. However, in fibronectin-rich microenvironment, α5 integrin promoted cell dispersion. Ligand-occupied α5 integrin and fibronectin were distributed in fibril-like pattern at cell-cell junction of evading cells, forming cell-cell fibrillar adhesions. Activated focal adhesion kinase was not present in these adhesions but was progressively relocalized with α5 integrin as cell migrates away from the spheroids. α5 integrin function in GBM appears to be more complex than previously suspected. As GBM overexpressed fibronectin, it is most likely that in vivo, α5-mediated dissemination from the tumor mass overrides α5-mediated tumor cell cohesion. In this respect, α5-integrin antagonists may be useful to limit GBM invasion in brain parenchyma.

Original languageEnglish
Pages (from-to)328-338
Number of pages11
JournalCancer Letters
Volume376
Issue number2
DOIs
Publication statusPublished - Jul 1 2016

Keywords

  • Fibronectin
  • Focal adhesion kinase
  • Glioblastoma
  • Integrin
  • Migration

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Blandin, A. F., Noulet, F., Renner, G., Mercier, M. C., Choulier, L., Vauchelles, R., Ronde, P., Carreiras, F., Etienne-Selloum, N., Vereb, G., Lelong-Rebel, I., Martin, S., Dontenwill, M., & Lehmann, M. (2016). Glioma cell dispersion is driven by α5 integrin-mediated cell-matrix and cell-cell interactions. Cancer Letters, 376(2), 328-338. https://doi.org/10.1016/j.canlet.2016.04.007