title: Immunohistochemical validation and expression profiling of NKG2D ligands in a wide spectrum of human epithelial neoplasms.
abstract: The MHC class I-chain-related proteins (MICs) and the UL16-binding proteins (ULBPs) are inducible stress response molecules that work as activators of a specific receptor, NKG2D, which is expressed on effector cells, such as NK cells and subsets of T cells. In this study, we sought to explore the biological significance of NKG2D ligands in human neoplasms by comprehensively examining the immunohistochemical expression profile of NKG2D ligands in a variety of human epithelial neoplasms. Following careful validation of the immunohistochemical specificity and availability of anti-human ULBP antibodies for formalin-fixed paraffin-embedded (FFPE) materials, the expression of NKG2D ligands was analyzed in FFPE tissue microarrays comprising 22 types of epithelial neoplastic tissue with their non-neoplastic counterpart from various organs. Hierarchical cluster analysis demonstrated a positive relationship among ULBP2/6, ULBP3, ULBP1, and ULBP5, whose expression patterns were similar across all of the neoplastic tissues examined. In contrast, MICA/B, as well as ULBP4, did not appear to be related to any other ligand. These expression profiles of NKG2D ligands in human neoplasms based on well-validated specific antibodies, followed by hierarchical cluster analysis, should help to clarify some functional aspects of these molecules in cancer biology, and also provide a path to the development of novel tumor-type-specific treatment strategies.
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan (HF, YH, YS, KCH, TM, YM)|Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan (HF, YS, NO, KF, MK)
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fujita
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan (HF, YH, YS, KCH, TM, YM)
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hatanaka
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan (HF, YH, YS, KCH, TM, YM)|Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan (HF, YS, NO, KF, MK)
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sutoh
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan (HF, YH, YS, KCH, TM, YM)
authors.forename: Yuta
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Translational Research and Clinical Trial Center, Hokkaido University Hospital, Sapporo, Japan (KO)
authors.forename: Koji
authors.initials: K
authors.lastname: Oba
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan (HF, YH, YS, KCH, TM, YM)
authors.forename: Kanako C
authors.initials: KC
authors.lastname: Hatanaka
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan (HF, YH, YS, KCH, TM, YM)
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mitsuhashi
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan (HF, YS, NO, KF, MK)
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Otsuka
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan (HF, YS, NO, KF, MK)
authors.forename: Kazunori
authors.initials: K
authors.lastname: Fugo
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan (HF, YS, NO, KF, MK)
authors.forename: Masanori
authors.initials: M
authors.lastname: Kasahara
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan (HF, YH, YS, KCH, TM, YM)
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsuno
mesh_terms: D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D002522:Chlorocebus aethiops; D058851:GPI-Linked Proteins / Q000032:analysis / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology*; D011485:Protein Binding
chemical_list: D002352:Carrier Proteins; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C488760:RAET1E protein, human; C423231:ULBP1 protein, human; C423230:ULBP2 protein, human; C423229:ULBP3 protein, human
keywords: NKG2D ligands; epithelial neoplasms; immunohistochemistry