TY - JOUR
T1 - Downregulation of major histocompatibility complex antigens in invading glioma cells
T2 - Stealth invasion of the brain
AU - Zagzag, David
AU - Salnikow, Konstantin
AU - Chiriboga, Luis
AU - Yee, Herman
AU - Lan, Li
AU - Ali, M. Aktar
AU - Garcia, Roberto
AU - Demaria, Sandra
AU - Newcomb, Elizabeth W.
N1 - Funding Information:
We thank Eugene Lukyanov and Greg Radin for their help in preparing the manuscript. This work was supported by a Grant from the National Institutes of Health (to DZ) R01 CA100426-01A1.
PY - 2005/3
Y1 - 2005/3
N2 - 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.
AB - 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.
KW - Gene chip
KW - Gliomas
KW - Invasion
KW - Laser capture microdissection
KW - Major histocompatibility complex
KW - Microarray analysis
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U2 - 10.1038/labinvest.3700233
DO - 10.1038/labinvest.3700233
M3 - Article
C2 - 15716863
AN - SCOPUS:14744292280
SN - 0023-6837
VL - 85
SP - 328
EP - 341
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 3
ER -