Premium
MMP9 mediates MICA shedding in human osteosarcomas
Author(s) -
Sun Dahui,
Wang Xu,
Zhang Haixia,
Deng Lijuan,
Zhang Yan
Publication year - 2011
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1042/cbi20100431
Subject(s) - nkg2d , ectodomain , mica , mmp9 , cleavage (geology) , mhc class i , immunosurveillance , matrix metalloproteinase , microbiology and biotechnology , chemistry , cancer research , biology , immune system , major histocompatibility complex , immunology , cytotoxicity , biochemistry , in vitro , receptor , downregulation and upregulation , gene , paleontology , fracture (geology)
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.