1. ¹Microvascular and Molecular Neuro-oncology Laboratory, New York University School of Medicine, New York, NY, USA
2. ²Department of Pathology, New York University School of Medicine, New York, NY, USA
3. ³Division of Neuropathology, New York University School of Medicine, New York, NY, USA
4. ⁴Department of Neurosurgery, New York University School of Medicine, New York, NY, USA
5. ⁵New York University Cancer Institute, New York University School of Medicine, New York, NY, USA
6. ⁶National Cancer Institute, NIH, Frederick, MD, USA

Correspondence: Dr D Zagzag, MD, PhD, Department of Pathology, Division of Neuropathology, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA. E-mail: dz4@nyu.edu

Received 14 July 2004; Revised 24 November 2004; Accepted 30 November 2004; Published online 31 January 2005.

Abstract

Invasion into surrounding brain tissue is a fundamental feature of gliomas and the major reason for treatment failure. The process of brain invasion in gliomas is not well understood. Differences in gene expression and/or gene products between invading and noninvading glioma cells may identify potential targets for new therapies. To look for genes associated with glioma invasion, we first employed Affymetrix microarray Genechip^® technology to identify genes differentially expressed in migrating glioma cells in vitro and in invading glioma cells in vivo using laser capture microdissection. We observed upregulation of a variety of genes, previously reported to be linked to glioma cell migration and invasion. Remarkably, major histocompatiblity complex (MHC) class I and II genes were significantly downregulated in migrating cells in vitro and in invading cells in vivo. Decreased MHC expression was confirmed in migrating glioma cells in vitro using RT-PCR and in invading glioma cells in vivo by immunohistochemical staining of human and murine glioblastomas for 2 microglobulin, a marker of MHC class I protein expression. To the best of our knowledge, this report is the first to describe the downregulation of MHC class I and II antigens in migrating and invading glioma cells, in vitro and in vivo, respectively. These results suggest that the very process of tumor invasion is associated with decreased expression of MHC antigens allowing glioma cells to invade the surrounding brain in a 'stealth'-like manner.