Immunohistochemical Validation and Expression Profiling of NKG2D Ligands in a Wide Spectrum of Human Epithelial Neoplasms. (March 2015)

• Record Type: Journal Article
• Authors: Fujita, Hiromi; Hatanaka, Yutaka; Sutoh, Yoichi; Suzuki, Yuta; Oba, Koji; Hatanaka, Kanako C.; Mitsuhashi, Tomoko; Otsuka, Noriyuki; Fugo, Kazunori; Kasahara, Masanori; Matsuno, Yoshihiro
• Is Part Of: Journal of histochemistry and cytochemistry. Volume 63:Number 3(2015:Mar.)
• Page Start: 217
• Page End: 227
• Publication Date: 2015-03
• Subjects: NKG2D ligands -- immunohistochemistry -- epithelial neoplasms; Histochemistry -- Periodicals; Cytochemistry -- Periodicals; Histocytochemistry -- methods; Histological Techniques; 572.05
• DOI: 10.1369/0022155414563800
• Languages: English
• ISSNs: 0022-1554

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.