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

摘要: // Annika M. Bourgonje 1 , Anna C. Navis 2 Jan T.G. Schepens Kiek Verrijp Liesbeth Hovestad 3 Riet Hilhorst Sheila Harroch 4 Pieter Wesseling 2,5 William P.J. Leenders and Wiljan J.A.J. Hendriks Department of Cell Biology Radboud University Medical Center, Nijmegen, The Netherlands Pathology, Institute for Molecular Life Sciences, PamGene International BV, ’s-Hertogenbosch, Neuroscience, Institut Pasteur, Paris, France 5 VU Amsterdam, Correspondence: Hendriks, email: Keywords : PTPRZ1, diffuse infiltrative growth, signal transduction, cell migration, tyrosine phosphorylation, PDZ Received June 07, 2014 Accepted August 18, Published 19, Abstract Gliomas are primary brain tumors which surgical resection radiotherapy is difficult because the growth tumor into parenchyma. For development alternative, drug-based, therapies more insight in molecular processes that steer this typical morphodynamic behavior glioma cells needed. Protein phosphatase PTPRZ-B a transmembrane signaling molecule found to be strongly up-regulated specimens. We assessed contribution protein domains via lentiviral knock-down over-expression using clinically relevant xenografts their derived models. resulted reduced migration proliferation vitro also inhibited vivo . Interestingly, expression only extracellular segment was sufficient rescue migratory phenotype from knock-down. In contrast, effects on could reverted after re-expression variants contained its C-terminal binding domain. Thus, distinct differentially required cells, respectively. pathways therefore represent attractive therapeutic entry points combat these tumors.