RNA interference targeting protein tyrosine phosphatase zeta/receptor-type protein tyrosine phosphatase beta suppresses glioblastoma growth in vitro and in vivo.

Abstract

The protein tyrosine phosphatase zeta/receptor-type protein tyrosine phosphatase beta (PTPzeta/RPTPbeta) 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 PTPzeta/RPTPbeta. 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 PTPzeta/RPTPbeta. Stable siRNA transfection resulted in strong down-regulation of PTPzeta/RPTPbeta expression. When injected subcutaneously into nude mice, clones that expressed normal levels of PTPzeta/RPTPbeta (PTPzeta + clones) formed exponentially growing tumours, whereas tumour growth was almost completely abrogated for clones that expressed reduced PTPzeta/RPTPbeta levels (PTPzeta - clones). Similar results were obtained using an orthotopic intracerebral model. Proliferation of PTPzeta - cells in vitro was significantly reduced compared with that of control clones. Matrix-immobilized PTN stimulated the proliferation of PTPzeta + cells but not of PTPzeta - cells. Haptotactic migration induced by PTN was reduced for PTPzeta - clones compared with control clones. Our findings suggest that antagonization of PTPzeta/RPTPbeta expression can inhibit glioma growth in vivo and may thus represent a potentially promising treatment strategy.

• Authors: Ulrike Ulbricht, Carmen Eckerich, Regina Fillbrandt, Manfred Westphal, Katrin Lamszus
• Journal: Journal of neurochemistry (J Neurochem) Vol. 98 Issue 5 Pg. 1497-506 (Sep 2006) ISSN: 0022-3042 [Print] England
• PMID: 16923162 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glial Fibrillary Acidic Protein
• Nerve Tissue Proteins
• RNA, Small Interfering
• PTPRZ1 protein, human
• Protein Tyrosine Phosphatases
• Ptprz1 protein, mouse
• Receptor-Like Protein Tyrosine Phosphatases, Class 5

Topics

• Animals
• Blotting, Western (methods)
• Cell Count (methods)
• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Proliferation
• Down-Regulation (physiology)
• Glial Fibrillary Acidic Protein (metabolism)
• Glioblastoma (metabolism, pathology, physiopathology)
• Humans
• Immunohistochemistry (methods)
• Mice
• Mice, Nude
• Neoplasm Transplantation (methods)
• Nerve Tissue Proteins (genetics, metabolism)
• Protein Tyrosine Phosphatases (genetics, metabolism)
• RNA Interference (physiology)
• RNA, Small Interfering (pharmacology, physiology)
• Receptor-Like Protein Tyrosine Phosphatases, Class 5
• Statistics, Nonparametric
• Time Factors
• Transfection (methods)