title: MMP9 mediates MICA shedding in human osteosarcomas.
abstract: The MICA (MHC class I chain-related molecule A) is a ligand for the activating immunoreceptor NKG2D (natural killer group 2, member D). NKG2D recognizes MICA expressing at the cell surface for cell elimination. Although MICA is overexpressed in many kinds of tumours, tumour cells can cleverly escape immunosurveillance. One underlying mechanism for immunoescape is tumour-derived MICA shedding. In this study, we report that osteosarcoma-derived MICA results from proteolytic cleavage of MICA α3 ectodomain. sMICA (soluble MICA) might be released in the early stage of disease. A MMP9 (matrix metalloproteinase 9, gelatinase B)-specific inhibitor suppressed sMICA release, indicating that MMP9 is critically involved in the osteosarcoma-associated proteolytic release of sMICA, which facilitates tumour immune escape. Using a specific MMP inhibitor might represent a double-edged sword, where it can inhibit tumour invasion and restore antitumour immune response.
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital, Jilin University, Changchun, Peoples Republic of China.
authors.forename: Dahui
authors.initials: D
authors.lastname: Sun
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhang
authors.forename: Lijuan
authors.initials: L
authors.lastname: Deng
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D012516:Osteosarcoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology; D017434:Protein Structure, Tertiary
chemical_list: D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D061965:Matrix Metalloproteinase Inhibitors; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011480:Protease Inhibitors; D020780:Matrix Metalloproteinase 9