title: Characterization of signaling function and expression of HLA class I molecules in medulloblastoma.
abstract: Although known for the important function in the immune system, MHC class I molecules are increasingly ascribed an alternative role in modifying signal transduction. In medulloblastoma, HLA class I molecules are associated with poor prognosis, and can induce ERK1/2 activation upon engagement with ligands that bind to incompletely assembled complexes (so called open conformers). We here demonstrate that ERK1/2 activation in medulloblastoma can occur in the absence of endogenously synthesized β2m, formally excluding involvement of closed HLA class conformation. In addition, several experimental observations suggest that heterogeneity of HLA class I expression may be a reflection of the status of original cells before transformation, rather than a consequence of immune-based selection of HLA-loss mutants. These results contribute to our understanding of an immune system-independent role of HLA class I in the pathology of medulloblastoma, and cancer in general.
authors.affiliation: Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010-2970, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Smith
authors.forename: Mariarita
authors.initials: M
authors.lastname: Santi
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Rushing
authors.forename: Robert
authors.initials: R
authors.lastname: Cornelison
authors.forename: Tobey J
authors.initials: TJ
authors.lastname: MacDonald
authors.forename: Stanislav
authors.initials: S
authors.lastname: Vukmanovic
mesh_terms: D015153:Blotting, Western; D002469:Cell Separation; D002528:Cerebellar Neoplasms / Q000276:immunology* / Q000378:metabolism; D002531:Cerebellum / Q000254:growth & development* / Q000378:metabolism; D002675:Child, Preschool; D005333:Fetus; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008527:Medulloblastoma / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015395:Histocompatibility Antigens Class I
references.citation: Cancer Res. 2007 Jun 1;67(11):5471-8
references.pmid: 17545629
references.citation: Int J Cancer. 2001 Jan 20;95(1):23-8
references.pmid: 11241306
references.citation: J Immunol. 1989 Jun 1;142(11):3763-72
references.pmid: 2469725
references.citation: Immunogenetics. 1986;24(3):206-8
references.pmid: 2428745
references.citation: Bone Marrow Transplant. 2000 May;25 Suppl 2:S88-95
references.pmid: 10933198
references.citation: Cancer Immunol Immunother. 2006 Aug;55(8):891-9
references.pmid: 16187081
references.citation: Annu Rev Immunol. 1998;16:323-58
references.pmid: 9597133
references.citation: J Neuroimmunol. 2002 Oct;131(1-2):83-91
references.pmid: 12458039
references.citation: J Cell Biol. 1984 Feb;98(2):725-31
references.pmid: 6319431
references.citation: Int J Dev Neurosci. 2001 Feb;19(1):53-62
references.pmid: 11226755
references.citation: J Immunol. 2003 Aug 15;171(4):1918-26
references.pmid: 12902494
references.citation: Science. 1995 Jul 28;269(5223):549-52
references.pmid: 7624779
references.citation: Surg Neurol. 1988 Jun;29(6):435-42
references.pmid: 3259730
references.citation: Neuroreport. 1996 Nov 25;7(18):2951-5
references.pmid: 9116217
references.citation: J Transl Med. 2009 Jul 12;7:59
references.pmid: 19594892
references.citation: J Neuroimmunol. 1999 Nov 1;101(1):76-86
references.pmid: 10580816
references.citation: J Immunol. 1992 May 15;148(10):3202-9
references.pmid: 1374450
references.citation: Nature. 1995 May 25;375(6529):325-8
references.pmid: 7753197
references.citation: Nat Rev Neurosci. 2004 Jul;5(7):521-31
references.pmid: 15208694
references.citation: Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15203-8
references.pmid: 11752463
references.citation: J Exp Med. 1997 Jan 20;185(2):305-16
references.pmid: 9016879
references.citation: J Immunol. 1997 Apr 1;158(7):3189-96
references.pmid: 9120273
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6784-9
references.pmid: 19346486
references.citation: J Exp Med. 1994 Sep 1;180(3):841-50
references.pmid: 8064236
references.citation: Nature. 1984 Aug 23-29;310(5979):688-91
references.pmid: 6433204
references.citation: J Hematother Stem Cell Res. 2000 Dec;9(6):795-812
references.pmid: 11177592
references.citation: Am J Pathol. 2001 Oct;159(4):1219-24
references.pmid: 11583948
references.citation: Int J Cancer. 2006 Jan 1;118(1):6-10
references.pmid: 16003753
references.citation: Hum Immunol. 1986 Apr;15(4):347-56
references.pmid: 2422143
references.citation: Clin Exp Immunol. 1991 Apr;84(1):170-4
references.pmid: 2015708
references.citation: Mol Biol Cell. 1997 Dec;8(12):2463-74
references.pmid: 9398668
references.citation: Int J Cancer. 2005 Nov 1;117(2):248-55
references.pmid: 15900607
references.citation: Cancer Immunol Immunother. 2007 Feb;56(2):227-36
references.pmid: 16783578
references.citation: Eur J Immunol. 1994 Sep;24(9):2115-23
references.pmid: 7916294
references.citation: Arch Immunol Ther Exp (Warsz). 2001;49(3):195-201
references.pmid: 11478393
references.citation: PLoS One. 2007 Dec 26;2(12):e1354
references.pmid: 18159237
references.citation: Neurol Med Chir (Tokyo). 1990 Sep;30(9):649-55
references.pmid: 1708454
references.citation: J Exp Med. 1986 Aug 1;164(2):458-73
references.pmid: 3088207
references.citation: Neuron. 1998 Sep;21(3):505-20
references.pmid: 9768838
references.citation: Science. 2000 Dec 15;290(5499):2155-9
references.pmid: 11118151
references.citation: Nature. 1995 May 25;375(6529):328-31
references.pmid: 7753198
references.citation: J Immunol. 1994 Apr 1;152(7):3353-60
references.pmid: 8144921
references.citation: Eur J Immunol. 1987 Sep;17(9):1257-63
references.pmid: 2443365
references.citation: Neurosci Lett. 1988 Sep 23;92(1):8-13
references.pmid: 3185980
references.citation: Cancer Res. 2000 Dec 1;60(23):6617-22
references.pmid: 11118044
references.citation: Eur J Neurosci. 1999 Dec;11(12):4468-72
references.pmid: 10594675
references.citation: Curr Opin Neurol. 1999 Dec;12(6):681-5
references.pmid: 10676748
references.citation: J Neuroimmunol. 1989 Feb;21(2-3):117-23
references.pmid: 2913044
references.citation: Invest Ophthalmol Vis Sci. 2001 Sep;42(10):2153-6
references.pmid: 11527924
references.citation: J Neuropathol Exp Neurol. 1970 Oct;29(4):583-600
references.pmid: 5471923
references.citation: Science. 1996 Nov 15;274(5290):1133-8
references.pmid: 8895456
references.citation: Cell Immunol. 1992 Jun;142(1):103-13
references.pmid: 1586951
references.citation: Cell. 1994 Aug 26;78(4):535-8
references.pmid: 8069904
references.citation: J Comp Neurol. 1978 May 1;179(1):223-44
references.pmid: 8980725
references.citation: Cancer Immunol Immunother. 2003 Jan;52(1):1-9
references.pmid: 12536234
references.citation: Proc Natl Acad Sci U S A. 1986 Aug;83(16):6007-11
references.pmid: 3090548
references.citation: Nature. 1984 Jul 19-25;310(5974):246-9
references.pmid: 6462208
references.citation: Cancer Res. 2005 Dec 1;65(23):11146-55
references.pmid: 16322265
references.citation: Int Immunol. 2003 Mar;15(3):331-9
references.pmid: 12618477
references.citation: Mod Pathol. 1995 Apr;8(3):333-8
references.pmid: 7617661
references.citation: J Biol Chem. 2004 Dec 17;279(51):53062-70
references.pmid: 15471856
references.citation: Trends Immunol. 2007 Mar;28(3):115-23
references.pmid: 17261379
references.citation: Curr Biol. 2003 Mar 4;13(5):394-400
references.pmid: 12620187
references.citation: J Comp Neurol. 1970 Aug;139(4):473-500
references.pmid: 4195699
references.citation: Cell. 2003 Mar 7;112(5):607-18
references.pmid: 12628182
references.citation: Proc Natl Acad Sci U S A. 1984 Oct;81(20):6476-80
references.pmid: 6436814