1. ¹AGY Therapeutics, Inc., 290 Utah Avenue, South San Francisco, CA 94080, USA
2. ²Department of Neurosurgery, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany

Correspondence: S Müller, E-mail: sabine@agyinc.com

Received 5 November 2002; Revised 30 April 2003; Accepted 7 May 2003.

Abstract

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 phosphatase (RPTP) and one of its ligands, pleiotrophin (Ptn). We confirmed by Northern blot analysis and immunohistochemistry that RPTP is enriched in tumor samples. Knockdown of RPTP by RNA interference studies established a functional role of RPTP in cell migration. Our results suggest a novel function for RPTP in regulating glioblastoma cell motility and point to the therapeutic utility of RPTP as a target for antibody-mediated therapy of brain tumors.