Downregulation of major histocompatibility complex antigens in invading glioma cells: Stealth invasion of the brain

David Zagzag, Konstantin Salnikow, Luis Chiriboga, Herman Yee, Li Lan, M. Aktar Ali, Roberto Garcia, Sandra Demaria, Elizabeth W. Newcomb

Research output: Contribution to journalArticle

92 Citations (Scopus)

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 β2 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.

Original languageEnglish (US)
Pages (from-to)328-341
Number of pages14
JournalLaboratory Investigation
Volume85
Issue number3
DOIs
StatePublished - Mar 2005

Fingerprint

Histocompatibility Antigens
Major Histocompatibility Complex
Glioma
Down-Regulation
Brain
Genes
Laser Capture Microdissection
MHC Class I Genes
MHC Class II Genes
Histocompatibility Antigens Class I
Histocompatibility Antigens Class II
Glioblastoma
Treatment Failure
Cell Movement
Up-Regulation
Staining and Labeling
Technology

Keywords

  • Gene chip
  • Gliomas
  • Invasion
  • Laser capture microdissection
  • Major histocompatibility complex
  • Microarray analysis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Downregulation of major histocompatibility complex antigens in invading glioma cells : Stealth invasion of the brain. / Zagzag, David; Salnikow, Konstantin; Chiriboga, Luis; Yee, Herman; Lan, Li; Ali, M. Aktar; Garcia, Roberto; Demaria, Sandra; Newcomb, Elizabeth W.

In: Laboratory Investigation, Vol. 85, No. 3, 03.2005, p. 328-341.

Research output: Contribution to journalArticle

Zagzag, D, Salnikow, K, Chiriboga, L, Yee, H, Lan, L, Ali, MA, Garcia, R, Demaria, S & Newcomb, EW 2005, 'Downregulation of major histocompatibility complex antigens in invading glioma cells: Stealth invasion of the brain', Laboratory Investigation, vol. 85, no. 3, pp. 328-341. https://doi.org/10.1038/labinvest.3700233
Zagzag, David ; Salnikow, Konstantin ; Chiriboga, Luis ; Yee, Herman ; Lan, Li ; Ali, M. Aktar ; Garcia, Roberto ; Demaria, Sandra ; Newcomb, Elizabeth W. / Downregulation of major histocompatibility complex antigens in invading glioma cells : Stealth invasion of the brain. In: Laboratory Investigation. 2005 ; Vol. 85, No. 3. pp. 328-341.
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