Role of cancer-associate fibroblasts on the regulation of angiognesis and bone resorption

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293429
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Okayama University
• Principal Investigator: SASAKI AKIRA 岡山大学, 医歯(薬)学総合研究科, 教授 (00170663)
• Co-Investigator(Kenkyū-buntansha): 岸本 晃治 岡山大学, 医歯(薬)学総合研究科, 助教 (40243480) ; 志茂 剛 岡山大学, 医歯(薬)学総合研究科, 准教授 (40362991) ; 吉岡 徳枝 岡山大学, 医歯(薬)学総合研究科, 助教 (50362984) ; 伊原木 聰一郎 岡山大学, 医歯(薬)学総合研究科, 助教 (80549866)
• Research Collaborator: OKUI Tatsuo ; MORISAWA Ayaka ; MASUI Masanori
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 血管新生阻害薬 / 骨破壊 / 破骨細胞 / 骨微小環境 / 口腔扁平上皮癌 / 癌関連線維芽細胞 / 口腔扁平上皮癌

Outline of Final Research Achievements

In the bone microenvironment of cancer induced bone destruction, the cancer-related fibroblasts play an important role on the regulation between angiogenesis and osteoclast formation and activity.
As a result, exhaustive genetic analysis of cancer-related fibroblasts in bone, we showed that these cells highly express the RANKL and angiogenesis factor (VEGF, MMPs, IL-X, TNF,PGE, etc.).
The copper ion regulator, ammonium tetrathiomolybdate (TM), which was candidates from screening of various angiogenesis inhibitors, inhibited the osteoclasts formation of the oral cancer bone destruction model and reinforced antitumor effect of Cetuximab in cancer bone destruction. In vitro study, TM inhibited osteoclasts formation through the suppression of angiogenesis and RANKL expression in osteoblast and osteocytes.

Free Research Field

外科系歯学