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RNA interference targeting protein tyrosine phosphatase ζ/receptor‐type protein tyrosine phosphatase β suppresses glioblastoma growth in vitro and in vivo
Author(s) -
Ulbricht Ulrike,
Eckerich Carmen,
Fillbrandt Regina,
Westphal Manfred,
Lamszus Katrin
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04022.x
Subject(s) - protein tyrosine phosphatase , pleiotrophin , biology , transfection , phosphatase , cell growth , in vivo , small interfering rna , in vitro , rna interference , microbiology and biotechnology , cell culture , receptor , tyrosine , cancer research , signal transduction , growth factor , phosphorylation , rna , biochemistry , gene , genetics
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.