Intracellular and extracellular domains of protein tyrosine phosphatase PTPRZ-B differentially regulate glioma cell growth and motility

Annika M. Bourgonje, Anna C. Navis, Jan T.G. Schepens, Kiek Verrijp, Liesbeth Hovestad, Riet Hilhorst, Sheila Harroch, Pieter Wesseling, William P.J. Leenders, Wiljan J.A.J. Hendriks

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Gliomas are primary brain tumors for which surgical resection and radiotherapy is difficult because of the diffuse infiltrative growth of the tumor into the brain parenchyma. For development of alternative, drug-based, therapies more insight in the molecular processes that steer this typical growth and morphodynamic behavior of glioma cells is needed. Protein tyrosine phosphatase PTPRZ-B is a transmembrane signaling molecule that is found to be strongly up-regulated in glioma specimens. We assessed the contribution of PTPRZ-B protein domains to tumor cell growth and migration, via lentiviral knock-down and over-expression using clinically relevant glioma xenografts and their derived cell models. PTPRZ-B knock-down resulted in reduced migration and proliferation of glioma cells in vitro and also inhibited tumor growth in vivo. Interestingly, expression of only the PTPRZ-B extracellular segment was sufficient to rescue the in vitro migratory phenotype that resulted from PTPRZ-B knock-down. In contrast, PTPRZ-B knock-down effects on proliferation could be reverted only after re-expression of PTPRZ-B variants that contained its C-terminal PDZ binding domain. Thus, distinct domains of PTPRZ-B are differentially required for migration and proliferation of glioma cells, respectively. PTPRZ-B signaling pathways therefore represent attractive therapeutic entry points to combat these tumors.

Original languageEnglish
Pages (from-to)8690-8702
Number of pages13
JournalOncotarget
Volume5
Issue number18
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Cell migration
  • Diffuse infiltrative growth
  • PDZ
  • PTPRZ1
  • Signal transduction
  • Tyrosine phosphorylation

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