title: A novel role of HLA class I in the pathology of medulloblastoma.
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, 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.
  
  
  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 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.
  
  
  CONCLUSIONS
  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.
authors: Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, Washington, DC, USA. smithco@mlhs.org
authors: Courtney
authors: C
authors: Smith
authors: Mariarita
authors: M
authors: Santi
authors: Bhargavi
authors: B
authors: Rajan
authors: Elisabeth J
authors: EJ
authors: Rushing
authors: Mi Rim
authors: MR
authors: Choi
authors: Brian R
authors: BR
authors: Rood
authors: Robert
authors: R
authors: Cornelison
authors: Tobey J
authors: TJ
authors: MacDonald
authors: Stanislav
authors: S
authors: Vukmanovic
mesh_terms: D000708:Anaplasia / Q000473:pathology; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000276:immunology / Q000473:pathology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008527:Medulloblastoma / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I; D016271:Proto-Oncogene Proteins c-myc; D048049:Extracellular Signal-Regulated MAP Kinases; D017493:Leukocyte Common Antigens