A novel role of HLA class I in the pathology of medulloblastoma

• Published in: Journal of translational medicine Vol. 7; no. 1; p. 59
• Main Authors: Smith, Courtney, Santi, Mariarita, Rajan, Bhargavi, Rushing, Elisabeth J, Choi, Mi Rim, Rood, Brian R, Cornelison, Robert, MacDonald, Tobey J, Vukmanovic, Stanislav
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12-07-2009; BioMed Central; BMC
• Subjects: Anaplasia - pathology; Biomarkers, Tumor - immunology; Biomarkers, Tumor - metabolism; Cancer; Cell Line, Tumor; Cerebellar Neoplasms - immunology; Cerebellar Neoplasms - pathology; Development and progression; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Histocompatibility antigens; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; HLA histocompatibility antigens; Humans; Immunohistochemistry; Leukocyte Common Antigens - metabolism; Major histocompatibility complex; Medulloblastoma; Medulloblastoma - immunology; Medulloblastoma - pathology; Physiological aspects; Prognosis; Proto-Oncogene Proteins c-myc - metabolism; United States
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/1479-5876-7-59

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.
We investigated expression of four essential components of MHC class I (heavy chain, beta2m, 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.
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 beta2m 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.
MHC class I expression in medulloblastoma is associated with anaplasia and c-myc expression, markers of poor prognosis. Peptide- and/or beta2m-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.