Midkine promotes oral cancer bone pain and progression

• Project/Area Number: 16H06992
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: Okayama University
• Principal Investigator: Okui Tatsuo 岡山大学, 大学病院, 助教 (40610928)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 癌性骨痛 / 癌骨転移 / 癌 / 骨転移 / 知覚神経 / 口腔癌 / 歯学

Outline of Final Research Achievements

we studied cancer bone pain in an intratibial mouse xenograft model that employs midkine positive human oral cancer cells.Mice intratibially injected with midkine positive oral cancer cells SAS developed characteristic osteolytic lesions on X-ray photograph.
Midkine antagonist iMDK dramatically reduced cancer bone pain and progression of cancer cells in bone in mouse model. MIdkine antagonist iMDK dramatically suppressed osteoclast differentiation from bone marrow cells via vitamin D3 and MCSF stimulation.

Research Products

• [Journal Article] The Prognostic Implications of Bone Invasion in Gingival Squamous Cell Carcinoma (2018)
  • Author(s): Shoko Yoshida, Tsuyoshi Shimo, Yurika Murase, KiyoFumi Takabatake, Koji Kishimoto, Soichiro Ibaragi, Norie Yoshioka, Tatsuo Okui, Hitoshi Nagatsuka AND Akira Sasaki
  • Journal Title: Anticancer Research Volume: 38 Issue: 2 Pages: 955-962
  • DOI: 10.21873/anticanres.12309
  • Peer Reviewed / Open Access
• [Journal Article] Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma. (2018)
  • Author(s): Morisawa A, Okui T, Shimo T, Ibaragi S, Okusha Y, Ono M, Nguyen TTH, Hassan NMM, Sasaki A.
  • Journal Title: International Journal of Oncology Volume: 52 Pages: 989-999
  • DOI: 10.3892/ijo.2018.4242
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Low-intensity pulsed ultrasound stimulation promotes osteoblast differentiation through hedgehog signaling (2018)
  • Author(s): Matsumoto Kenichi、Shimo Tsuyoshi、Kurio Naito、Okui Tatsuo、Ibaragi Soichiro、Kunisada Yuki、Obata Kyoichi、Masui Masanori、Pai Pang、Horikiri Yuu、Yamanaka Nobuyuki、Takigawa Masaharu、Sasaki Akira
  • Journal Title: J. Cell Biochem. Volume: 印刷中 Issue: 6 Pages: 4352-4360
  • DOI: 10.1002/jcb.26418
  • Peer Reviewed
• [Journal Article] Oral Squamous Cell Carcinoma-derived Sonic Hedgehog Promotes Angiogenesis (2017)
  • Author(s): Kuroda H, Kurio N, Shimo T, Matsumoto K, Masui M, Takabatake K, Okui T, Ibaragi S, Kunisada Y, Obata K, Yoshioka N, Kishimoto K, Nagatsuka H, Sasaki A.
  • Journal Title: Anticancer Research Volume: 37 Issue: 12 Pages: 6731-6737
  • DOI: 10.21873/anticanres.12132
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of Neurokinin 3 Receptor Signaling in Oral Squamous Cell Carcinoma. (2017)
  • Author(s): Obata K, Shimo T, Okui T, Matsumoto K, Takada H, Takabatake K, Kunisada Y, Ibaragi S, Yoshioka N, Kishimoto K, Nagatsuka H, Sasaki A.
  • Journal Title: Anticancer Research Volume: 37 Issue: 11 Pages: 6119-6123
  • DOI: 10.21873/anticanres.12060
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma. (2017)
  • Author(s): Takada H, Ibaragi S, Eguchi T, Okui T, Obata K, Masui M, Morisawa A, Takabatake K, Kawai H, Yoshioka N, Hassan NMM, Shimo T, Hu GF, Nagatsuka H, Sasaki A.
  • Journal Title: International Journal of Oncology Volume: 51 Issue: 2 Pages: 625-32
  • DOI: 10.3892/ijo.2017.4050
  • NAID: 120006370695
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bone Pain Induced by Multiple Myeloma Is Reduced by Targeting V-ATPase and ASIC3. (2017)
  • Author(s): Hiasa M, Okui T, Allette YM, Ripsch MS, Sun-Wada GH, Wakabayashi H, Roodman GD, White FA, Yoneda T
  • Journal Title: Cancer Research Volume: 77(6) Issue: 6 Pages: 1283-1295
  • DOI: 10.1158/0008-5472.can-15-3545
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tachykinin Receptor 3 Distribution in Human Oral Squamous Cell Carcinoma. (2016)
  • Author(s): Obata K1, Shimo T, Okui T, Matsumoto K, Takada H, Takabatake K, Kunisada Y, Ibaragi S, Nagatsuka H, Sasaki A.
  • Journal Title: Anti cancer research Volume: 36(12) Issue: 12 Pages: 6335-6341
  • DOI: 10.21873/anticanres.11230
  • Peer Reviewed / Open Access
• [Presentation] TRPV1 を通じて興奮した知覚神経は HGF 産生により骨内でのがんの進展および骨 からの二次転移を促進する (2017)
  • Author(s): 奥井達雄，日浅雅博，志茂 剛，Fletcher A White，G. David Roodman，佐々木朗，米田俊之
  • Organizer: 第61回（公社）日本口腔外科学会総会
• [Presentation] Neuronal HGF regulates breast cancer progression and bone pain induction (2017)
  • Author(s): Tatsuo Okui, Masahiro Hiasa, Fletcher White, G David Roodman, Toshiyuki Yoneda.
  • Organizer: 44th European Calcified Tissue Society Congress
• [Presentation] Bone pain-modifying actions of osteocytes via connexin43-mediated communications with sensory nerves (2017)
  • Author(s): Masahiro Hiasa, Tatsuo Okui, Jesu´ s Delgado-Calle, Teresita Bellido, G David Roodman, Fletcher White, Lilian Plotkin, Toshiyuki Yoneda
  • Organizer: 44th European Calcified Tissue Society Congress