title: Downregulation of major histocompatibility complex antigens in invading glioma cells: stealth invasion of the brain.
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 beta2 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.
authors.affiliation: Microvascular and Molecular Neuro-oncology Laboratory, New York University School of Medicine, New York, NY, USA. dz4@nyu.edu
authors.forename: David
authors.initials: D
authors.lastname: Zagzag
authors.forename: Konstantin
authors.initials: K
authors.lastname: Salnikow
authors.forename: Luis
authors.initials: L
authors.lastname: Chiriboga
authors.forename: Herman
authors.initials: H
authors.lastname: Yee
authors.forename: Li
authors.initials: L
authors.lastname: Lan
authors.forename: M Aktar
authors.initials: MA
authors.lastname: Ali
authors.forename: Roberto
authors.initials: R
authors.lastname: Garcia
authors.forename: Sandra
authors.initials: S
authors.lastname: Demaria
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Newcomb
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D015536:Down-Regulation; D005353:Fibronectins / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D012313:RNA / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D005353:Fibronectins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D012313:RNA