The role of S100A8/A9-Emmprin in the metastasis of melanoma cells.

• Project/Area Number: 15K09788
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Tokyo Medical University
• Principal Investigator: TSUBOI RYOJI 東京医科大学, 医学部, 主任教授 (70221421)
• Co-Investigator(Kenkyū-buntansha): 原田 和俊 東京医科大学, 医学部, 准教授 (20324197) ; 山本 真実 (田中 真実 / 山本真実) 東京医科大学, 医学部, 助教 (60421062) ; 前 賢一郎 東京医科大学, 医学部, 助教 (60532257)
• Co-Investigator(Renkei-kenkyūsha): SAKAGUCHI MASAKIYO 岡山大学, 大学院医薬学総合研究科 細胞生物学, 准教授 (70379840)
• Research Collaborator: MAEDA TETSUO 東京医科大学, 医学部, 技術員 ; EGUSA CHIZU 東京医科大学, 医学部, 技術員 ; HIBINO TOSHIHIKO 資生堂, リサーチセンター
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: メラノーマ / 転移 / S100A8/9 / S100A8/A9 / 転移モデル / S100A9 / Emmprin / 転移抑制物質

Outline of Final Research Achievements

The S100 protein family, especially S100A8 and S100A9, mediates the inflammatory reaction and is involved in the proliferation and metastasis of cancer cells. Emmprin (extracellular matrix metalloproteinase inducer) and neuroplastin b are S100A8/A9 receptors on the surface of keratinocytes. Immunohistological analysis of melanomas revealed that Emmprin was expressed at both the invasive edge of lesions and the adjacent skin. Tail vein-injected, highly Emmprin-expressing melanoma cells（SK-MEL2）metastasized to the skin of epidermis-specific S100A9 transgenic mice. In our recent study, a C57/BL6 mouse model of pulmonary metastasis from primary cutaneous melanoma (B16-F10 cells) was established to assess metastasis quantitatively by MRI. A model using S100A9 transgenic mice will be deployed to analyze metastasis of SK-MEL2 melanoma cells. ELISA screening failed to detect a molecule inhibiting the binding of S100A9 with recombinant Emmprin fixed on a plate.

Research Products

• [Journal Article] Reduced expression of the ATP2A2 gene in vemurafenib-induced keratoacanthoma-like papules in a melanoma patient. (2017)
  • Author(s): Wakimoto H, Harada K, Arai T, Maeda T, Irisawa R, Tsuboi R
  • Journal Title: Int J Dermatol Volume: 56 Issue: 2
  • DOI: 10.1111/ijd.13430
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] N-Ras mutation in vemurafenib-associated expanding melanocytic nevus (2017)
  • Author(s): Harada Kazutoshi、Kato Yuichiro、Maeda Tatsuo、Yoshida Maki、Irisawa Ryokichi、Nagao Toshitaka、Tsuboi Ryoji
  • Journal Title: The Journal of Dermatology Volume: 44 Issue: 5
  • DOI: 10.1111/1346-8138.13670
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A pulmonary metastatic model of murine melanoma assessed by magnetic resonance imaging. (2017)
  • Author(s): Numata T, Kiryu S, Maeda T, Egusa C, Tsuboi R, Harada K
  • Journal Title: Exp Dermatol Volume: Epub ahead Issue: 7 Pages: 619-621
  • DOI: 10.1111/exd.13327
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] A pulmonary metastatic model of murine melanoma assessed by magnetic resonance imaging. (2017)
  • Author(s): Numata T, Kiryu S, Maeda T, Egusa C, Tsuboi R, Harada K.
  • Organizer: The 42nd Annual Meeting of the Japanese Society for Investigative Dermatology