Antimetastatic effects of a soluble IL-33 receptor and its utility as a prognostic biomarker in colorectal cancer.

• Project/Area Number: 24791422
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Shimane University
• Principal Investigator: AKIMOTO Miho 島根大学, 医学部, 助教 (60437556)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 転移抑制 / がん微小環境 / 大腸がん / サイトカイン / 予後予測

Outline of Final Research Achievements

Our studies revealed that the expression of sST2, a soluble receptor for IL-33, in human and mouse colorectal cancer cells suppress sporadic metastasis via modulating inflammatory tumormicroenvironments. Importantly, the administration of recombinant sST2 showed antitumor and antimetastatic effects in human or mouse colon tumor-bearing mice. Our results also indicated that ST2 expression levels in tumor tissues may be an effective prognostic biomarker in colon cancer. Collectively, our studies demonstrate the potential for developing novel ST2-based therapeutic and diagnostic strategies for colorectal cancer.

Research Products

• [Journal Article] Anticancer Effect of Ginger Extract Against Pancreatic Cancer Cells Mainly Through Reactive Oxygen Species-Mediated Autotic Cell Death (2015)
  • Author(s): Miho Akimoto, Mari Iizuka, Rie Kanematsu, Masato Yoshida, Keizo Takenaga
  • Journal Title: PLOS ONE Volume: 未定
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Attenuation of reactive oxygen species by antioxidants suppresses hypoxia-induced epithelial-mesenchymal transition and metastasis of pancreatic cancer cells (2013)
  • Author(s): Shimojo Y, Akimoto M, Hisanaga T, Tanaka T, Tajima Y, Honma Y, Takenaga K.
  • Journal Title: Clin Exp Metastasis Volume: 30(2) Issue: 2 Pages: 143-54
  • DOI: 10.1007/s10585-012-9519-8
  • Peer Reviewed
• [Journal Article] Antitumor effect of Japanese apricot extract (MK615) on human cancer cells in vitro and in vivo through a reactive oxygen species-dependent mechanism (2013)
  • Author(s): Hattori M, Kawakami K, Akimoto M, Takenaga K, Suzumiya J, Honma Y.
  • Journal Title: Tumori Volume: 99(2) Pages: 239-48
  • Peer Reviewed
• [Journal Article] An inhibitor of HIF-α subunit expression suppresses hypoxia-induced dedifferentiation of human NSCLC into cancer stem cell-like cells (2013)
  • Author(s): Akimoto M, Nagasawa H, Hori H, Uto Y, Honma Y, Takenaga K.
  • Journal Title: World J Med Genet Volume: 3(4) Issue: 4 Pages: 41-54
  • DOI: 10.5496/wjmg.v3.i4.41
  • Peer Reviewed
• [Presentation] 可溶性ST2は炎症性のがん微小環境を修飾し膵がんの増殖を抑制する (2014)
  • Author(s): 秋元 美穂、竹永 啓三
  • Organizer: 第12回 がんとハイポキシア研究会
  • Place of Presentation: ホテルマリターレ創世（佐賀）
  • Year and Date: 2014-11-21 – 2014-11-22
• [Presentation] HIF-2αの阻害はヒト膵がん細胞のTRAIL感受性を増強する (2014)
  • Author(s): 原嶋 奈々江、秋元 美穂、竹永 啓三、原田 守
  • Organizer: 第12回 がんとハイポキシア研究会
  • Place of Presentation: ホテルマリターレ創世（佐賀）
  • Year and Date: 2014-11-21 – 2014-11-22
• [Presentation] Soluble ST2 modulates inflammatory tumor microenvironment and inhibits neoan giogenesis and growth of pancreatic cancer (2014)
  • Author(s): Miho Akimoto, Mamoru Harada, Keizo Takenaga
  • Organizer: 第73回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Enhancement of glycolysis and survival of lung carcinoma cells with mtDNA mutation co-cultured with stromal cells (2014)
  • Author(s): Keizo Takenaga, Miho Akimoto
  • Organizer: 第73回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Inhibition of HIF-2α sensitizes human pancreatic cancer cells to TRAIL (2014)
  • Author(s): Nanae Harashima, Yoko Hari, Hiroyuki Monma, Miho Akimoto, Keizo Takenaga, Yoshitsugu Tajima, Mamoru Harada
  • Organizer: 第73回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 膵臓がん細胞に対する生姜抽出物の抗腫瘍効果 (2014)
  • Author(s): 兼松里衣、秋元美穂、竹永敬三
  • Organizer: 日本生薬学会 第61回年会
  • Place of Presentation: 福岡大学（福岡）
  • Year and Date: 2014-09-13 – 2014-09-14
• [Presentation] 可溶性IL-33受容体ST2による炎症性微小環境の修飾を介した大腸がんの転移の抑制 (2013)
  • Author(s): 秋元美穂、竹永啓三
  • Organizer: 第22回 日本がん転移学会学実総会・集会
  • Place of Presentation: ホテルブエナビスタ松本（松本）
• [Presentation] Soluble ST2 inhibits tumor growth and metastasts of colon carcinoma cells by modulating inflammatory microenvironment (2013)
  • Author(s): Miho Akimoto, Yoshio Honma, Keizo Takenaga
  • Organizer: 第72回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(横浜）
• [Presentation] 可溶性IL-33受容体sST2による炎症性微小環境の修飾を介した大腸がんの転移の抑制 (2013)
  • Author(s): 秋元美穂、竹永啓三
  • Organizer: 第22回日本がん転移学会学術集会・総会
  • Place of Presentation: ホテルブエナビスタ松本（松本市）
• [Presentation] Inhibition of tumor growth and metastasis of colon carcinoma cells by sST2 (2012)
  • Author(s): Miho Akimoto, Yoshio Honma, Keizo Takenaga
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ホテルロイトン札幌（札幌市）
• [Presentation] N-Acetylcysteine suppresses hypoxia-induced EMT and hepatic metastasis of human pancreatic cancer cells (2012)
  • Author(s): Yoshihide Shimojo, Miho Akimoto, Yoshitsugu Tajima, Yoshio Honma, Keizo Takenaga
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ホテルロイトン札幌（札幌市）
• [Remarks] 島根大学 医学部 生命科学講座 腫瘍生物学
  • URL: http://www.med.shimane-u.ac.jp/llt/index.html
• [Remarks] 島根大学 医学部 生命科学講座 腫瘍生物学
  • URL: http://www.med.shimane-u.ac.jp/llt/index.html