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Keywords:

  • glioma;
  • invasion;
  • migration;
  • phosphacan;
  • pleiotrophin;
  • proliferation

Abstract

The protein tyrosine phosphatase ζ/receptor-type protein tyrosine phosphatase β (PTPζ/RPTPβ) and its ligand pleiotrophin (PTN) are overexpressed in human glioblastomas. Both molecules are involved in neuronal cell migration during CNS development. In addition, PTN can induce glioma cell migration which is at least in part mediated through binding to PTPζ/RPTPβ. To study the relevance of this ligand–receptor pair for glioma growth in vitro and in vivo, we transfected the human glioblastoma cell line U251-MG with small interfering RNA (siRNA) directed against PTPζ/RPTPβ. Stable siRNA transfection resulted in strong down-regulation of PTPζ/RPTPβ expression. When injected subcutaneously into nude mice, clones that expressed normal levels of PTPζ/RPTPβ (PTPζ + clones) formed exponentially growing tumours, whereas tumour growth was almost completely abrogated for clones that expressed reduced PTPζ/RPTPβ levels (PTPζ – clones). Similar results were obtained using an orthotopic intracerebral model. Proliferation of PTPζ – cells in vitro was significantly reduced compared with that of control clones. Matrix-immobilized PTN stimulated the proliferation of PTPζ + cells but not of PTPζ – cells. Haptotactic migration induced by PTN was reduced for PTPζ – clones compared with control clones. Our findings suggest that antagonization of PTPζ/RPTPβ expression can inhibit glioma growth in vivo and may thus represent a potentially promising treatment strategy.