ANTITUMOR EFFECT OF SCLEROSTIN AGAINST MALIGNANT BONE TUMOR

• Project/Area Number: 18K16651
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Shinshu University
• Principal Investigator: Okamoto Masanori 信州大学, 医学部附属病院, 助教(特定雇用) (50596781)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 骨肉腫 / 悪性骨腫瘍 / 抗がん剤 / Wnt経路 / スクレロスチン / Wnt

Outline of Final Research Achievements

Sclerostin suppressed the proliferative capacity and migratory ability of osteosarcoma cells. The osteosarcoma model mice showed inhibited tumor growth and prolonged survival periods. Because sclerostin is not a cytocidal agent, the effect of its combined use with existing anticancer drugs such as doxorubicin should be investigated for future clinical applications.

Academic Significance and Societal Importance of the Research Achievements

悪性骨腫瘍の中で最も頻度の高い骨肉腫は、組織学的に腫瘍性の類骨・骨を形成する悪性腫瘍と定義される。腫瘍の多様性、不均一性が高く、原因遺伝子変異は特定されていない。また骨肉腫に対して有効な治療薬は30年以上新規開発がなされておらず、新規抗がん剤の開発が切望されている。
骨形成は全ての骨肉腫に唯一共通する現象であり、スクレロスチンはその骨形成を抑制する。本研究の成果により、スクレロスチンが骨肉腫に対して抗腫瘍効果を持つことが明らかになった。
スクレロスチンの性質・骨組織特異性を逆手に取り、骨肉腫に対する創薬研究にブレークスルーを起こし、骨肉腫に対しての新規治療薬の開発を目指す。

Research Products

• [Journal Article] A Review of T-Cell Related Therapy for Osteosarcoma (2020)
  • Author(s): Yoshida Kazushige、Okamoto Masanori、Aoki Kaoru、Takahashi Jun、Saito Naoto
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 14 Pages: 4877-4877
  • DOI: 10.3390/ijms21144877
  • Peer Reviewed / Open Access
• [Presentation] THERAPEUTIC EFFECT OF SCLEROSTIN ON OSTEOSARCOMA (2019)
  • Author(s): Masanori Okamoto, Kazushige Yoshida, Jun Sasaki, Kaoru Aoki, Munehisa Kito, Yasuo Yoshimura, Shuichiro Suzuki, Atsushi Tanaka, Akira Takazawa, Hisao Haniu, Takashi Takizawa, Atsushi Sobajima, Takayuki Kamanaka, Naoto Saito, Hiroyuki Kato
  • Organizer: RCOST 2019(The 41st Annual Meeting of the Royal College of Orthopaedic Surgeons of Thailand)
  • Int'l Joint Research / Invited
• [Presentation] 骨肉腫に対する古典的Wntシグナル阻害因子スクレロスチンの抗腫瘍効果 (2018)
  • Author(s): 岡本正則
  • Organizer: 第51回日本整形外科学会骨・軟部腫瘍学術集会
• [Presentation] Antitumor effect of sclerostin against osteosarcoma (2018)
  • Author(s): Masanori Okamoto
  • Organizer: EMSOS 2018 (31st Annual Meeting of The European Musculo-Skeletal Oncology Society)
  • Int'l Joint Research
• [Presentation] Antitumor effect of sclerostin against osteosarcoma (2018)
  • Author(s): Masanori Okamoto
  • Organizer: APMSTS 2018 (12th Asia Pacific Musculo Skeletal Tumor Society meeting)
  • Int'l Joint Research
• [Presentation] THERAPEUTIC EFFECT OF SCLEROSTIN ON OSTEOSARCOMA (2018)
  • Author(s): Masanori Okamoto
  • Organizer: CTOS 2018 (2018 Connective Tissue Oncology Society Annual Meeting)
  • Int'l Joint Research