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Journal of Neuro-Oncology

, Volume 103, Issue 2, pp 197–206 | Cite as

Characterization of signaling function and expression of HLA class I molecules in medulloblastoma

  • Courtney Smith
  • Mariarita Santi
  • Elisabeth J. Rushing
  • Robert Cornelison
  • Tobey J. MacDonald
  • Stanislav Vukmanovic
Laboratory Investigation - Human/Animal Tissue

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.

Keywords

HLA Medulloblastoma Cerebellum Signaling 

Abbreviations

β2m

β2 microglobulin

IHC

Immunohistochemistry

TAP

Transporter associated with antigen processing

Notes

Acknowledgments

This work was partially supported by national Institutes of Health grant (R01 CA111835) awarded to TJM.

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Courtney Smith
    • 1
    • 3
  • Mariarita Santi
    • 2
  • Elisabeth J. Rushing
    • 4
  • Robert Cornelison
    • 5
  • Tobey J. MacDonald
    • 1
    • 3
  • Stanislav Vukmanovic
    • 1
    • 3
  1. 1.Center for Cancer and Immunology Research, Children’s Research InstituteChildren’s National Medical CenterWashingtonUSA
  2. 2.Department of PathologyChildren’s National Medical CenterWashingtonUSA
  3. 3.Department of PediatricsGeorge Washington University School of MedicineWashingtonUSA
  4. 4.Department of NeuropathologyArmed Forces Institute of PathologyWashingtonUSA
  5. 5.Cancer Genetics BranchNational Human Genome Research Institute NIHBethesdaUSA

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