Understanding molecular mechanism underlying innate immune system escape for metastasis in sarcoma

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10458
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: 382661 (2016-2017); Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses (2015)
• Principal Investigator: Sasagawa Satoru 医療法人徳洲会野崎徳洲会病院(附属研究所), 研究所, 部長 (80345115)
• Research Collaborator: ITOH Kazuyuki 医療法人徳洲会野崎徳洲会病院, 検診センター, センター長 (20301806)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 滑膜肉腫 / 転移

Outline of Final Research Achievements

In this study，we focused on the mechanism how the synovial sarcoma cells escape from immune surveillance and found that MICA/B molecules in synovial sarcoma cells were disappeared when the cells were in hypoxia and floating conditions. Twist1 transcription factor also depressed MICA/B expression. On the other hand, low-dose of HDAC inhibitors markedly up-regulated MICA/B expression. MICA/B expression was N-glycosylation sensitive and tunicamycin treatment rapidly killed MICA/B expression. We also found that MICA/B negative synovial sarcoma cells was also sensitive to HDAC inhibitor treatment and confirmed weak MICA/B protein expression. Here, we found that MICA/B mRNA sequence in MICA/B negative cells were not uniform and most of that disrupted N-glycosylation site in protein level. In conclusion, low-dose of HDAC inhibitor treatment could improve anti-tumor-effect by NK cells by MICA/B stimulation.

Free Research Field

分子腫瘍学