Analysis of ameloblastoma tumor microenvironment and development of novel therapies

• Project/Area Number: 25893141
• 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: TAKEBE Yuichiro 岡山大学, 医歯(薬)学総合研究科, 助教 (00714677)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: エナメル上皮腫 / CCN2 / 腫瘍間質

Outline of Final Research Achievements

35 paraffin-embedded ameloblastoma cases, ameloblastoma-derived cell lines (AM-1) and primary cultures of ameloblastoma stromal fibroblasts were used. Immunohistochemistry, Western blot and RT-PCR were performed. Parenchyma-stromal CCN2 overexpression correlated significantly with fibrous-type compared to myxoid-type stroma, suggesting a role in fibrosis .Recombinant CCN2 induction of enhanced ASF proliferation in AM-1 medium supports this view.Results suggest that effects of secreted growth factors are governed by ameloblastoma parenchyma-stromal interactions. CCN2 promotes fibrogenesis independent of TGF-β signaling. Its ablation is associated with a phenotypic switch to a myxoid-type microenvironment, conducive for TGF-β/BMP4 signaling to promote osteoclastogenesis.

Research Products

• [Journal Article] A case of adenoid cystic carcinoma associated with IgG4-related disease (2015)
  • Author(s): Shimo T, Yao M, Takebe Y, Ono Y, Obata K, Kurio N, Ibaragi S, Yoshioka N, Kishimoto K, Yanagi Y, Nagatsuka H, Sasaki A
  • Journal Title: Int J Surg Case Rep Volume: 10 Pages: 12-16
  • DOI: 10.1016/j.ijscr.2015.01.022
  • Peer Reviewed / Open Access
• [Journal Article] Expression and roles of CCN2 in dental mesenchymal cells in primary culture-With findings in a case of odontogenic myxofibroma. (2014)
  • Author(s): Shimo T, Koyama E, Horikiri Y, Okui T, Kurio N, Katase N, Yoshida S, Takebe Y, Kishimoto K, Yoshioka N, Nagatsuka H, Sasaki A
  • Journal Title: Oral Sci Int. Volume: 11巻1号 Issue: 1 Pages: 8-14
  • DOI: 10.1016/s1348-8643(13)00008-6
  • Peer Reviewed / Open Access
• [Journal Article] Expression and roles of CCN2 in dental mesenchymal cells in primary culture-With findings in a case of odontogenic myxofibroma (2014)
  • Author(s): SHIMO Tsuyoshi
  • Journal Title: Oral Sci Int Volume: 11 Pages: 8-14
  • Peer Reviewed
• [Journal Article] Establishment of odontoblastic cells, which indicate odontoblast features both in vivo and in vitro (2013)
  • Author(s): Tsujigiwa H, Katase N, Lefeuvre M, Yamachika E, Tamamura R, Ito S, Takebe Y, Matsuda H, Nagatsuka H
  • Journal Title: J Oral Pathol Med Volume: 42(10) Issue: 10 Pages: 799-806
  • DOI: 10.1111/jop.12080
  • Peer Reviewed
• [Presentation] エナメル上皮腫におけるCCN2およびYAPの局在とその役割 (2014)
  • Author(s): 武部祐一郎 河合穂高 藤井昌江 高畠清文 辻極秀次 長塚仁
  • Organizer: 岡山歯学会
  • Place of Presentation: 岡山大学、岡山
  • Year and Date: 2014-10-26
• [Presentation] Analyze of variation of the tumor stroma by ameloblastoma cells. (2014)
  • Author(s): Yuichiro Takebe
  • Organizer: Annual meeting of society for regenerative hard tissue biology
  • Place of Presentation: Chung Shan Medical University, Taiwan
  • Year and Date: 2014-08-21
• [Presentation] LOH analysis in 1p36 region and the immunohistochemical analysis of RIZ1 expression in oral squamous cell carcinoma (2014)
  • Author(s): TAMAMURA Ryo 、KANNO Takeshi 、TAKEBE Yuichiro、KAWAI Hotaka、OKADA Hiroyuki、NAGATSUKA Hitoshi
  • Organizer: Annual meeting of society for regenerative hard tissue biology
  • Place of Presentation: Chung Shan Medical University, Taiwan
  • Year and Date: 2014-08-21
• [Presentation] エナメル上皮腫におけるCCN2の発現解析 (2014)
  • Author(s): 河合穂高 武部祐一郎 片瀬直樹 于淞 藤井昌江 高畠清文 辻極秀次 長塚仁
  • Organizer: 日本病理学会
  • Place of Presentation: 広島国際会議場、広島
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 口腔扁平上皮癌における1p36領域のLOH解析およびRIZ1発現の検討 (2014)
  • Author(s): 玉村亮
  • Organizer: 日本病理学会
  • Place of Presentation: 広島
• [Presentation] エナメル上皮腫腫瘍細胞における成長因子の発現と腫瘍間質に関する検討 (2013)
  • Author(s): 武部祐一郎
  • Organizer: 口腔外科学会 総会
  • Place of Presentation: 福岡
• [Presentation] エナメル上皮腫における成長因子の発現と腫瘍間質への影響 (2013)
  • Author(s): 武部祐一郎
  • Organizer: 歯科基礎医学会 総会
  • Place of Presentation: 岡山