Roles of oxidized LDL receptor and TLR4 signaling in lung metastasis

• Project/Area Number: 23590347
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: TOMITA Takeshi 東京女子医科大学, 医学部, 助教 (20302242)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 血清アミロイドA3 / 酸化LDL受容体 / TLR4 / 血清アミロイド / S100A8

Research Abstract

Tumor metastasis happens results of various steps including formation of pre-matastatic phase. In the pre-metastatic lungs, accumulations of myeloid derived suppressor cells and upregulations of S100A8 and SAA3 expressions have been observed, but detailed molecular mechanisms are not fully understood. This study focused on oxidized LDL receptor and TLR/MD-2 complex, both express in lung endothelial cells and epithelial cells in relation with their potential endogenous ligands, S100A8 and SAA3. By using purified proteins and overexpression sytems, the research identified that SAA3 binds MD-2 but not TLR4. In addition certain SAA3 variant binds oxidized LDL receptor.

Research Products

• [Journal Article] ADAM12-cleaved ephrin-A1 contributes to lung metastasis (2014)
  • Author(s): Ieguchi K., TOMITA T., Omori T., Komatsu A., Deguchi A., Masuda J., Duffy S., Coulthard M., Boyd A., Maru Y.
  • Journal Title: Oncogene Volume: (in press)
• [Journal Article] ADAM12-cleaved ephrin-A1 contributes to lung metastasis. (2014)
  • Author(s): Ieguchi K, Tomita T, Omori T, Komatsu A, Deguchi A, Masuda J, Duffy SL, Coulthard MG, Boyd A, Maru Y.
  • Journal Title: Oncogene Volume: 未定 Issue: 17 Pages: 2179-90
  • DOI: 10.1038/onc.2013.180
  • Peer Reviewed / Open Access
• [Journal Article] Ephrin-A1 expression induced by S100A8 is mediated by the toll-like receptor 4 (2013)
  • Author(s): Ieguchi K., Omori T., Komatsu A., TOMITA T., Deguchi A., Maru Y.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 440 Pages: 623-629
• [Journal Article] Serum amyloid A3 binds MD-2 to activate p38 and NF-κB pathways in a MyD88-dependent manner (2013)
  • Author(s): Deguchi A., TOMITA T., Omori T., Komatsu A., Ohto U., Takahashi S., Tanimura N., Akashi-Takamura S., Miyake K., Maru Y.
  • Journal Title: J. Immunol Volume: 191 Pages: 1856-1864
• [Journal Article] Primary tumours modulate innate immune signalling to create pre-metastatic vascular hyperpermeability foci (2013)
  • Author(s): Hiratsuka S., Ishibashi S., TOMITA T., Watanabe A., Akashi-Takamura S., Murakami M., Kijima H., Miyake K., Aburatani H., Maru Y.
  • Journal Title: Nat. Commun Volume: 4 Pages: 1853-1853
• [Journal Article] Ephrin-A1 expression induced by S100A8 is mediated by the toll-like receptor 4 (2013)
  • Author(s): Ieguchi K, Omori T, Komatsu A, Tomita T, Deguchi A, Maru Y
  • Journal Title: Biochem Biophys Res Commun Volume: 440(4) Issue: 4 Pages: 623-629
  • DOI: 10.1016/j.bbrc.2013.09.119
  • Peer Reviewed
• [Journal Article] Serum Amyroid A3 binds MD-2 to activates p38 and NF-kB pathway in a MyD88-dependent manner (2013)
  • Author(s): Deguchi A, Tomita T, Omori T, Komatsu A, Ohto U, Takahashi S, Tanimura N, Akashi-Takamura S, Miyake K, Maru Y
  • Journal Title: J Immunol Volume: 191(4) Issue: 4 Pages: 1856-1864
  • DOI: 10.4049/jimmunol.1201996
  • Peer Reviewed
• [Presentation] 肺転移での転移前土壌形成における自然免疫の役割 (2013)
  • Author(s): 富田毅, 平塚佐千枝, 丸義朗
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 肺転移におけるephrin-A1とADAM12の機能解析 (2013)
  • Author(s): 家口勝昭, 富田毅, 丸義朗
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 肺転移での転移前土壌形成における自然免疫の役割 (2013)
  • Author(s): 富田 毅、平塚佐千枝、丸 義朗
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 肺転移におけるephrin-A1とADAM12の機能解析 (2013)
  • Author(s): 家口勝昭、富田 毅、丸 義朗
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Imbalance of Clara-cell mediated homeostatic inflammation is involved in lung metastasis (2011)
  • Author(s): Tomita T
  • Organizer: 第13回TNF国際会議
  • Place of Presentation: 淡路市
• [Presentation] lung metastasis and homeostatic inflammation mediated by lung epithelial cells (2011)
  • Author(s): 富田毅, 丸義朗
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 肺上皮細胞による自然炎症と転移 (2011)
  • Author(s): 富田 毅、丸 義朗
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋