Development of new therapies targeting SHH in oral cancer jaw bone destruction and its application to personalized medicine

• Project/Area Number: 26293428
• 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: Tsuyoshi Shimo 岡山大学, 医歯(薬)学総合研究科, 准教授 (40362991)
• Co-Investigator(Kenkyū-buntansha): 吉岡 徳枝 岡山大学, 医歯(薬)学総合研究科, 助教 (50362984) ; 栗尾 奈愛 岡山大学, 大学病院, 医員 (80622141)
• Co-Investigator(Renkei-kenkyūsha): KURIO Naito 岡山大学, 大学病院, 医員 (80622141)
• Research Collaborator: NAGATSUKA Hitoshi 岡山大学, 医歯薬学総合研究科, 教授 (70237535)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000); Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
• Keywords: 口腔扁平上皮癌 / 破骨細胞 / ヘッジホッグ / ソニックヘッジホッグ / 顎骨浸潤 / 癌骨破壊 / 癌顎骨破壊 / 破骨細胞分化

Outline of Final Research Achievements

Oral squamous cell carcinoma frequently invades into the maxilla and the mandible, and that is associated with a worse prognosis. Sonic hedgehog (SHH) signaling contributes to the development, we found that SHH was not expressed in normal oral gingiva, but highly expressed in tumor cells that had invaded the bone matrix. On the other hand, the hedgehog receptor and the signaling molecule were highly expressed in the osteoclasts and the progenitor cells. SHH stimulated osteoclast formation and pit formation, and the GPCR is involved in the signaling.

Research Products

• [Int'l Joint Research] The Children's Hospital of Philadelphia(米国)
• [Int'l Joint Research] China Medical University(China)
• [Int'l Joint Research] The Children's Hospital of Philadelphia(米国)
• [Journal Article] Expression and role of sonic hedgehog in the process of fracture healing with aging (2016)
  • Author(s): Kenichi Matsumoto, Tsuyoshi Shimo, Naito Kurio, Tatsuo Okui, Kyoichi Obata, Masanori Masui, Pai Pang, Yuu Horikiri, Akira Sasaki
  • Journal Title: In Vivo Volume: 30 Pages: 99-105
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction. (2016)
  • Author(s): Shimo T, Matsumoto K, Takabatake K, Aoyama E, Takebe Y, Ibaragi S, Okui T, Kurio N, Takada H, Obata K, Pang P, Iwamoto M, Nagatsuka H, Sasaki A.
  • Journal Title: PLoS One. Volume: 11(3) Issue: 3 Pages: e0151731-e0151731
  • DOI: 10.1371/journal.pone.0151731
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Detection of sonic hedgehog in a patients undergoing with orthognathic surgery (2016)
  • Author(s): Yuki Kunisada, Tsuyoshi Shimo, Masanori Masui, Norie Yoshioka, Soichiro Ibaragi, Kenichi Matsumoto, Tatsuo Okui, Naito Kurio, Shohei Domae, Koji Kishimoto, Akiyoshi Nishiyama, Akira Sasaki
  • Journal Title: International Journal of Surgery Open Volume: 5 Pages: 1-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tachykinin Receptor 3 Distribution in human oral squamous cell carcinoma (2016)
  • Author(s): Kyoichi Obata, Tsuyoshi Shimo, Tatsuo Okui, Kenichi Matsumoto, Hiroyuki Takada, Kiyofumi Takabatake, Yuki Kunisada, Soichiro Ibaragi, Hitoshi Nagatsuka, Akira Sasaki
  • Journal Title: Anticancer Research Volume: 36 Pages: 6335-6341
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Novel Midkine Inhibitor iMDK Inhibits Tumor Growth and Angiogenesis in Oral Squamous Cell Carcinoma (2016)
  • Author(s): Masui M, Okui T, Shimo T, Takabatake K, Fukazawa T, Matsumoto K, Kurio N, Ibaragi S, Naomoto Y, Nagatsuka H, Sasaki A.
  • Journal Title: Anticancer Research Volume: 36 Pages: 2775-2781
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Synthetic Terrein Inhibits Progression of Head and Neck Cancer by Suppressing Angiogenin Production (2016)
  • Author(s): Shibata A, Ibaragi S, Mandai H, Tsumur a T, Kishimoto K, Okui T, Hassan NM, Shimo T, Omori K, Hu GF, Takashiba S, Suga S, Sasaki A
  • Journal Title: Anticancer Research Volume: 36 Pages: 2161-2168
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Expression Pattern of Sonic Hedgehog Signaling and Calcitonin Gene Related Peptide in the Socket Healing Process after Tooth Extraction (2015)
  • Author(s): Pai Pang, Tsuyoshi Shimo, Hiroyuki Takada, Kenichi Matsumoto, Norie Yoshioka, Soichiro Ibaragi, Akira Sasaki
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 27 Issue: 1 Pages: 353-356
  • DOI: 10.1016/j.bbrc.2015.09.139
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 骨破壊病変と骨格形成因子 (2016)
  • Author(s): 志茂 剛
  • Organizer: 第13回日本病理学会カンファレンス
  • Place of Presentation: 六甲山ホテル
  • Invited
• [Presentation] Neurokinin B 受容体の口腔扁平上皮癌における発現の検討 (2016)
  • Author(s): 小畑協一，志茂 剛，高田紘行，高畠清文，奥井達雄，伊原木聰一郎，長塚 仁，佐々木 朗
  • Organizer: 第64回日本口腔科学会中国・四国地方部会
  • Place of Presentation: 山口
• [Presentation] Expression Pattern of Sonic Hedgehog Signaling and Calcitonin Gene Related Peptide in the Socket Healing Process after Tooth Extraction (2015)
  • Author(s): Pai Pang, Tsuyoshi Shimo, Hiroyuki Takada, Kenichi Matsumoto, Norie Yoshioka, Soichiro Ibaragi, Akira Sasaki
  • Organizer: 12th National Conference on Oral and Maxillofacial Surgery in Conjunction with joint of China-Japan Joint Conference on Oral and Maxillofacial Surgery
  • Place of Presentation: Shanghai, China
  • Year and Date: 2015-09-24
  • Int'l Joint Research
• [Presentation] Hedgehog signaling in jawbone invasion of oral squamous cell carcinoma (2015)
  • Author(s): Tsuyoshi Shimo, Kenichi Matsumoto, Eriko Aoyama, Yuichiro Takebe, Takabatake Kiyofumi, Soichiro Ibaragi, Tatsuo Okui, Naito Kurio, Pang Pai, Hitoshi Nagatsuka, Akira Sasaki
  • Organizer: ASBMR 2015 Annual Meeting
  • Place of Presentation: Seattle, WA, USA
  • Year and Date: 2015-09-09
  • Int'l Joint Research
• [Presentation] The mechanical stimulation mediate the osteoblast differentiation through hedgehog signaling (2015)
  • Author(s): Kenichi Matsumoto, Tsuyoshi Shimo, Naito Kurio, Tatsuo Okui, and Akira Sasaki
  • Organizer: ASBMR 2015 Annual Meeting
  • Place of Presentation: Seattle, WA, USA
  • Year and Date: 2015-09-09
  • Int'l Joint Research
• [Presentation] Expression and role of sonic hedgehog in oral squamous cell carcinoma induced jaw bone destruction (2014)
  • Author(s): Tsuyoshi Shimo
  • Organizer: ASBMR Annual Meeting
  • Place of Presentation: Houston（米国）
  • Year and Date: 2014-09-15
• [Book] Analysis of pathological activities of CCN proteins in bone metastasis (2016)
  • Author(s): Tsuyoshi Shimo, Norie Yoshioka, Masaharu Takigawa, and Akira Sasaki
  • Total Pages: 576
  • Publisher: Springer Publishing Company, New York
• [Book] Protocol for measuring angiogenic activities of CCN proteins (2016)
  • Author(s): Tsuyoshi Shimo and Masaharu Takigawa
  • Total Pages: 576
  • Publisher: Springer Publishing Company, New York
• [Remarks] 破骨細胞性顎骨破壊におけるソニックヘッジホッグの役割
  • URL: http://www.jsbmr.jp/1st_author/196_tshimo.html