A novel role of HLA class I in the pathology of medulloblastomaReport as inadecuate




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Journal of Translational Medicine

, 7:59

First Online: 12 July 2009Received: 19 March 2009Accepted: 12 July 2009DOI: 10.1186-1479-5876-7-59

Cite this article as: Smith, C., Santi, M., Rajan, B. et al. J Transl Med 2009 7: 59. doi:10.1186-1479-5876-7-59

Abstract

BackgroundMHC class I expression by cancer cells enables specific antigen recognition by the immune system and protection of the host. However, in some cancer types MHC class I expression is associated with an unfavorable outcome. We explored the basis of MHC class I association with unfavorable prognostic marker expression in the case of medulloblastoma.

MethodsWe investigated expression of four essential components of MHC class I heavy chain, β2m, TAP1 and TAP2 in 10 medulloblastoma mRNA samples, a tissue microarray containing 139 medulloblastoma tissues and 3 medulloblastoma cell lines. Further, in medulloblastoma cell lines we evaluated the effects of HLA class I engagement on activation of ERK1-2 and migration in vitro.

ResultsThe majority of specimens displayed undetectable or low levels of the heavy chains. Medulloblastomas expressing high levels of HLA class I displayed significantly higher levels of anaplasia and c-myc expression, markers of poor prognosis. Binding of β2m or a specific antibody to open forms of HLA class I promoted phosphorylation of ERK1-2 in medulloblastoma cell line with high levels, but not in the cell line with low levels of HLA heavy chain. This treatment also promoted ERK1-2 activation dependent migration of medulloblastoma cells.

ConclusionMHC class I expression in medulloblastoma is associated with anaplasia and c-myc expression, markers of poor prognosis. Peptide- and-or β2m-free forms of MHC class I may contribute to a more malignant phenotype of medulloblastoma by modulating activation of signaling molecules such as ERK1-2 that stimulates cell mobility.

Abbreviationsβ2mβ2-microglobulin

IHCimmunohistochemistry

TAPtransporter associated with antigen processing.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-7-59 contains supplementary material, which is available to authorized users.

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Author: Courtney Smith - Mariarita Santi - Bhargavi Rajan - Elisabeth J Rushing - Mi Rim Choi - Brian R Rood - Robert Cornelison

Source: https://link.springer.com/







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