Investigation of collective molecular mechanisms in stemness and metastasis in sarcoma

2014 Fiscal Year Final Research Report

• Project/Area Number: 24791575
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses
• Principal Investigator: SASAGAWA Satoru 地方独立行政法人大阪府立病院機構大阪府立成人病センター(研究所), その他部局等, 研究員 (80345115)
• Co-Investigator(Renkei-kenkyūsha): ITOH Kazuyuki 大阪府立成人病センター研究所, 生物学部門, 部長 (20301806)
• Research Collaborator: YOSHIKAWA Hideki ; NAKA Norifumi ; ARAKI Nobuhito ; HAMADA Kenichiro ; JOYAMA Shin ; WAKAMATSU Toru ; TANAKA Takaaki
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 骨軟部腫瘍 / 転移

Outline of Final Research Achievements

Based on correlation between multipotency and metastatic activity in mouse osteosarcoma and human synovial sarcoma, we performed qPCR based molecular screening and identified Twist1 as a key molecule. In normal tissue, Twist1 commits cellular stemness, regulates differentiation into bone and cartilage, regulates cell migration, and responds to hypoxia condition. Indeed, Twist1 knockdown by siRNA in mouse osteosarcoma cell line significantly suppressed lung metastasis. Drug screening identified HDAC inhibitors which can suppress Twist1 expression mouse osteosarcoma cells and daily administration to mouse with osteosarcoma xenograft significantly inhibited lung metastasis. In addition, we found that Twist1 suppressed MICA/B expression in human synovial sarcoma cells. MICA/B are recognized by NK cells, resulting in elimination of tumor cells in the body. In conclusion, it is thought that Twist1 drives lung metastasis via regulating multiple cellular functions in sarcomas.

Free Research Field

分子腫瘍学