論文 - 詳細
| RRC ID | 51679 |
|---|---|
| 著者 | Shiraishi K, Mimura K, Kua LF, Koh V, Siang LK, Nakajima S, Fujii H, Shabbir A, Yong WP, So J, Takenoshita S, Kono K. |
| タイトル | Inhibition of MMP activity can restore NKG2D ligand expression in gastric cancer, leading to improved NK cell susceptibility. |
| ジャーナル | J Gastroenterol |
| Abstract |
BACKGROUND AND METHODS:Natural killer (NK) cells can react with tumor cells through the balance of inhibitory and stimulatory signals between NK cell surface receptors and their ligands, such as MHC class I chain-related A (MICA), MHC class I chain-related B (MICB), and several UL16-binding proteins (ULBPs). In the present study, we evaluated the relationship between NKG2D ligand expression and matrix metalloproteinase (MMP) activity in in vitro culture systems of a panel of gastric cancer cell lines (n = 10) and clinical samples (n = 102). RESULTS:First, the surface expression of NK group 2 member D (NKG2D) ligands (MICA, MICB, ULBP-2, and ULBP-3) on tumor cells was markedly downregulated on in vitro culture, in parallel to the upregulation of MMPs analyzed by gelatin zymography and gene expression microarray, whereas the transcript levels of NKG2D ligands remained unchanged on in vitro culture. Second, MMP-specific inhibitors could restore the downregulated expression of NKG2D ligands and functionally improve susceptibilities to NK cells in vitro. Third, the production of soluble NKG2D ligands was increased on in vitro culture and was inhibited by MMP-specific inhibitors. Finally, there was a significant inverse correlation between MMP-9 expression and NKG2D ligand expression as analyzed by immunohistochemistry in clinical tumor samples. CONCLUSION:The present study is a comprehensive study demonstrating that upregulation of MMP activity can induce a downregulation of expression of NKG2D ligands in gastric cancer cells, leading to lower-level susceptibility to NK cells. |
| 巻・号 | 51(12) |
| ページ | 1101-1111 |
| 公開日 | 2016-12-1 |
| DOI | 10.1007/s00535-016-1197-x |
| PII | 10.1007/s00535-016-1197-x |
| PMID | 27002316 |
| MeSH | Antigens, CD Cadherins / metabolism Cytotoxicity, Immunologic / drug effects Down-Regulation / immunology Gene Expression Regulation, Neoplastic / drug effects Gene Expression Regulation, Neoplastic / immunology Humans Killer Cells, Natural / immunology* Ligands Matrix Metalloproteinase 9 / metabolism Matrix Metalloproteinase Inhibitors / pharmacology Matrix Metalloproteinases / metabolism* NK Cell Lectin-Like Receptor Subfamily K / metabolism* Stomach Neoplasms / genetics Stomach Neoplasms / immunology Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology Tumor Cells, Cultured |
| IF | 5.561 |
| 引用数 | 11 |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) |