A novel role of HLA class I in the pathology of medulloblastoma
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BioMed Central
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A novel role of HLA class I in the pathology of medulloblastoma Courtney Smith1,3, Mariarita Santi2, Bhargavi Rajan1, Elisabeth J Rushing4, Mi Rim Choi1, Brian R Rood1,3, Robert Cornelison5, Tobey J MacDonald1,3 and Stanislav Vukmanovic*1,3 Address: 1Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC, USA, 2Department of Pathology, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC, USA, 3Department of Pediatrics, George Washington University School of Medicine, Washington, DC, USA, 4Department of Neuropathology, Armed Forces Institute of Pathology, Washington, DC, USA and 5Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA Email: Courtney Smith - [email protected]; Mariarita Santi - [email protected]; Bhargavi Rajan - [email protected]; Elisabeth J Rushing - [email protected]; Mi Rim Choi - [email protected]; Brian R Rood - [email protected]; Robert Cornelison - [email protected]; Tobey J MacDonald - [email protected]; Stanislav Vukmanovic* - [email protected] * Corresponding author
Published: 12 July 2009 Journal of Translational Medicine 2009, 7:59
doi:10.1186/1479-5876-7-59
Received: 19 March 2009 Accepted: 12 July 2009
This article is available from: http://www.translational-medicine.com/content/7/1/59 © 2009 Smith et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: MHC 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. Methods: We 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. Results: The 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 medull
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