A role for receptor tyrosine phosphatase zeta in glioma cell migration.
Glioblastomas (GBM) are the most frequent and malignant human brain tumor type. Typically striking in adulthood, tumor progression is rapid, relentless, and ultimately leads to the patient's death within a year of diagnosis. The identification of transcriptionally regulated genes can lead to the discovery of targets for antibody or small-molecule-mediated therapy, as well as diagnostic markers. We prepared cDNA arrays that are specifically enriched for genes expressed in human brain tumors and profiled gene expression patterns in 14 individual tumor samples. Out of 25,000 clones arrayed, greater than 200 genes were found transcriptionally induced in glioblastomas compared to normal human brain tissue including the receptor tyrosine phosphatasezeta (RPTPzeta) and one of its ligands, pleiotrophin (Ptn). We confirmed by Northern blot analysis and immunohistochemistry that RPTPzeta is enriched in tumor samples. Knockdown of RPTPzeta by RNA interference studies established a functional role of RPTPzeta in cell migration. Our results suggest a novel function for RPTPzeta in regulating glioblastoma cell motility and point to the therapeutic utility of RPTPzeta as a target for antibody-mediated therapy of brain tumors.
Müller
Sabine
S
AGY Therapeutics, Inc, 290 Utah Avenue, South San Francisco, CA 94080, USA. sabine@agyinc.com
Kunkel
Philip
P
Lamszus
Katrin
K
Ulbricht
Ulrike
U
Lorente
Gustavo Angel
GA
Nelson
April Michelle
AM
von Schack
David
D
Chin
Daniel J
DJ
Lohr
Scott Curtis
SC
Westphal
Manfred
M
Melcher
Thorsten
T
D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000201:enzymology*; D002465:Cell Movement; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D005910:Glioma / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism* / Q000502:physiology*; D012313:RNA / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D012333:RNA, Messenger; D012313:RNA; C516895:PTPRZ1 protein, human; D017027:Protein Tyrosine Phosphatases; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5