Analyses of signal network of bone metabolism through giant cell-rich lesions of bone

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19085
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Yokohama City University
• Principal Investigator: Kato Ikuma 横浜市立大学, 医学部, 助教 (80644939)
• Research Collaborator: FURUYA Mitsuko ; KAWABATA Yusuke ; MATSUO Kosuke ; TANAKA Reiko ; OHASHI Kenichi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 骨巨細胞腫

Outline of Final Research Achievements

Denosumab, a human monoclonal antibody directed against the receptor activator of nuclear factor-kappa B ligand (RANKL), was introduced as a therapeutic agentis for giant cell tumor of bone (GCTB). To understand the complete mechanism of denosumab, we compared the histologic and immunohistochemical features of GCTBs before and after denosumab therapy. In all cases, the osteoclast-like giant cells disappeared. However, all post-therapeutic lesions still contained many H3.3 G34W(+) cells. Immunofluorescent double-staining revealed that RUNX2(+) mononuclear cells co-expressed H3.3 G34W in pre- and post-denosumab lesions. In conclusion, the neoplastic cells survive denosumab therapy and make woven bones in respond to the new environment free from osteoclastic cells.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

近年発見された特異的遺伝子異常の視点を加えたことで、骨巨細胞腫は、非腫瘍細胞（破骨細胞系細胞）との相互作用によって成立している腫瘍性病変であることが明らかとなった。また抗RANKL抗体による治療は、一見すると劇的な治療効果があるように思われていたが、根本的な治療とは言い難いことが明らかとなった。病理組織像と遺伝子異常を統合的に解析することが、疾患の本質的な理解につながることが示された。