Molecular analysis of bone metastatic pain

• Project/Area Number: 24592363
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Wakayama Medical University (2013-2014); Osaka Medical College (2012)
• Principal Investigator: NAKANISHI Masako 和歌山県立医科大学, 医学部, 助教 (60437382)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 癌性疼痛 / 骨転移 / 動物モデル

Outline of Final Research Achievements

Gene expression analysis was performed using by dorsal root ganglions (DRG) of rat bone metastasis model. It was revealed that matrix metalloproteinase (MMP) 13 and P2x7 receptor were up-regulated in DRG with bone metastatic microenvironment. Cytokines such as IL-1 and TNF-a, abundant in bone metastatic foci, increased the MMP13 mRNA expression in organ cultured DRG. It was considered that up-regulated MMP13 expression accelerate the osteolysis, which in turn contribute tumor progression and development of pain. In addition, it was suggested that acidic microenvironment in tumor is one of the factors, which induced the expression of P2x7 receptors in DRG.

Research Products

• [Journal Article] 骨転移に伴う疼痛のメカニズム (2014)
  • Author(s): 中西雅子
  • Journal Title: 腎と骨代謝 Volume: 27 Pages: 41-46
• [Journal Article] Cyclooxygenase-2 expression is associated with vascular endothelial growth factor-c and lymph node metastasis in human oral tongue cancer (2014)
  • Author(s): Morita Y, Morita N, Hata K, Nakanishi M, Kimoto N, Omata T, Nakamura Y, Yoneda T
  • Journal Title: Oral Surg Oral Med Oral Pathol Oral Radiol Volume: 117(4) Issue: 4 Pages: 502-510
  • DOI: 10.1016/j.oooo.2013.12.410
  • Peer Reviewed
• [Journal Article] Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes (2013)
  • Author(s): Hata K, Takashima R, Amano K, Ono K, Nakanishi M, Yoshida M, Wakabayashi M, Matsuda A, Maeda Y, Suzuki Y, Sugano S, Whitson RH, Nishimura R and Yoneda T
  • Journal Title: Nature communications Volume: 4 Issue: 1 Pages: 2850-2860
  • DOI: 10.1038/ncomms3850
  • Peer Reviewed
• [Presentation] 骨転移巣の酸性環境はTrpv1の活性化によるCGRPの発現増加を介して疼痛に関与する (2014)
  • Author(s): 中西雅子、波多賢二、米田俊之、村垣泰光
  • Organizer: 第103回日本病理学会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-25 – 2014-04-27
• [Presentation] 酸性環境によるTrpv1の活性化はCGRPの発現増加を介して骨転移痛に関与する (2013)
  • Author(s): 中西雅子
  • Organizer: 第118回日本解剖学会
  • Place of Presentation: 高松
• [Presentation] 骨転移巣の酸性環境はTRPV1の活性化によるCGRPの発現増加を介して疼痛に関与する
  • Author(s): 中西雅子、波多賢二、米田俊之、村垣泰光
  • Organizer: 第103回日本病理学会
  • Place of Presentation: 広島
• [Book] 癌と骨 (2013)
  • Author(s): 中西雅子、波多賢二、米田俊之
  • Total Pages: 347
  • Publisher: メディカルレビュー社