Application of REIC/Dkk-3 gene therapy on gastrointestinal cancers targeting cancer stem cells

• Project/Area Number: 24591943
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Okayama University of Science
• Principal Investigator: KATAOKA Ken 岡山理科大学, 理学部, 准教授 (10293317)
• Co-Investigator(Kenkyū-buntansha): SAKAGUCHI Masakiyo 岡山大学, 医歯薬学総合研究科, 准教授 (70379840) ; MURATA Hitoshi 岡山大学, 医歯薬学総合研究科, 助教 (90579096)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: REIC/Dkk-3 / がん遺伝子治療 / 腸管上皮組織 / 皮膚組織 / TNF-α / 炎症 / がん幹細胞 / 組織幹細胞

Outline of Final Research Achievements

Detailed screening of REIC/Dkk-3 expression revealed that REIC/Dkk-3 was localized in stem cells niche of skin and intestinal epithelium. REIC/Dkk-3 expression was also observed in three-dimensional cultured Caco-2 spheroids. To identify factor(s) regulating REIC/Dkk-3 expression in keratinocytes, we screened growth factors and cytokines that were reported to involved in keratinocyte growth and differentiation. Only TNF-alpha could down-regulate REIC/Dkk-3 in normal skin keratinocytes among seven factors we screened. The data suggest that expression balance of REIC/Dkk-3 and TNF-alpha adjust the skin tissue (re)modeling by skin keratinocytes and endothelial cells.

Research Products

• [Journal Article] DNAX-activating protein 10 (DAP10) membrane adaptor associates with receptor for advanced glycation end products (RAGE) and modulates the RAGE-triggered signaling pathway in human keratinocytes (2014)
  • Author(s): Sakaguchi M, Murata H, Aoyama Y, Hibino T, Putranto EW, Ruma IM, Inoue Y, Sakaguchi Y, Yamamoto K, Kinoshita R, Futami J, Kataoka K, Iwatsuki K, Huh NH
  • Journal Title: J Biol Chem Volume: 289 Issue: 34 Pages: 23389-23402
  • DOI: 10.1074/jbc.m114.573071
  • NAID: 120006333870
  • Peer Reviewed / Open Access
• [Journal Article] SARM1 and TRAF6 bind to and stabilize PINK1 on depolarized mitochondria (2013)
  • Author(s): Murata H, Sakaguchi M, Kataoka K, Huh NH
  • Journal Title: Mol Biol Cell Volume: 24 Pages: 2772-2784
  • Peer Reviewed
• [Journal Article] Inhibition of RAGE signaling by intracellularly delivered-inhibitor peptides using PEI-cationization (2013)
  • Author(s): Putranto EW, Murata H, Yamamoto KI, Kataoka K, Yamada H, Futami J, Sakaguchi M, Huh NH
  • Journal Title: Int J Mol Med Volume: 32 Pages: 938-944
  • Peer Reviewed
• [Journal Article] Design, synthesis and in vitro apoptotic activity of a series of α-benzyl phenylpropanoic acid-type peroxisome proliferator-activated receptor (PPAR) gamma partial agonists with improved aqueous solubility (2013)
  • Author(s): Ohashi M, Oyama T, Putranto EW, Waku T, Nobusada H, Kataoka K, Matsuno K, Yashiro M, Morikawa K, Huh NH, Miyachi H
  • Journal Title: Bioorg Med Chem Volume: 21 Pages: 2319-2332
  • Peer Reviewed
• [Journal Article] DOCK7 is a critical regulator of RAGE-Cdc42 signaling axis that induces formation of dendritic pseudopodia in human cancer cells (2013)
  • Author(s): Yamamoto KI, Murata H, Putranto EW, Kataoka K, Motoyama A, Hibino T, Inoue Y, Sakaguchi M, Huh NH
  • Journal Title: Oncol Rep Volume: 29 Pages: 1073-1079
  • Peer Reviewed
• [Journal Article] Expression pattern of REIC/Dkk-3 in mouse squamous epithelia (2012)
  • Author(s): Kataoka K, Du G, Maehara N, Murata H, Sakaguchi M, Huh N
  • Journal Title: Clin Exp Dermatol Volume: 37 Pages: 428-431
  • Peer Reviewed
• [Journal Article] S100A7 promotes the migration and invasion of osteosarcoma cells via the receptor for advanced glycation end products (2012)
  • Author(s): Kataoka K, Ono T, Murata H, Morishita M, Yamamoto KI, Sakaguchi M, Huh NH
  • Journal Title: Oncol Lett Volume: 3 Pages: 1149-1153
  • Peer Reviewed
• [Journal Article] Partial sensitization of human bladder cancer cells to a gene-therapeutic adenovirus carrying REIC/Dkk-3 by down-regulation of BRPK/PINK1 (2012)
  • Author(s): 6. Jin Y, Murata H, Sakaguchi M, Kataoka K, Watanabe M, Nasu Y, Kumon H, Huh NH
  • Journal Title: Oncol Rep Volume: 27 Pages: 695-699
  • Peer Reviewed
• [Presentation] 貧血の診断治療における血球計数ﾃﾞｰﾀの応用・赤血球形態記載の有用性 (2014)
  • Author(s): 佐々木 真美、杉本 美香、西岡 樹、山本 友樹、田中 正信、片岡 健
  • Organizer: 第47回日本臨床衛生検査技師会中四国支部医学検査学会
  • Place of Presentation: ひめぎんホール（愛媛）
  • Year and Date: 2014-09-13 – 2014-09-14
• [Presentation] TNF-aによるREIC/Dkk-3の表皮細胞における発現制御と増殖・分化の関係 (2014)
  • Author(s): 綾部 雄基 、 鶴田 太輝 、 阪口 政清、 片岡 健
  • Organizer: 第9回日本臨床検査学教育学会学術大会
  • Place of Presentation: 大田区産業プラザ（東京）
  • Year and Date: 2014-08-20 – 2014-08-22
• [Presentation] Program for cell culturists and the instructors for cell culturing organized by the JTCA education & research committee (2014)
  • Author(s): 片岡 健、小原 有弘、鈴木 崇彦
  • Organizer: 日本組織培養学会第87回大会
  • Place of Presentation: 星陵会館（東京）
  • Year and Date: 2014-05-29 – 2014-05-30
• [Presentation] Tumor Necrosis Factor-alpha down-regulates a tumor suppressor gene, REIC/Dkk-3, in normal skin keratinocytes (2013)
  • Author(s): Kataoka K, Sakaguchi M, Murata H, Hashikawa N, Huh NH
  • Organizer: The 2013 In Vitro Biology Meeting
  • Place of Presentation: 米国
• [Presentation] Professional training for cell culture “Programs for beginners to experts” (2013)
  • Author(s): Furue-Kusuda M, Tsutsui T, Kataoka K
  • Organizer: 日本組織培養学会第86回大会
  • Place of Presentation: つくば市
• [Presentation] New Therapeutic Approaches to Cancer from In Vitro Studies (2012)
  • Author(s): Kataoka K
  • Organizer: The 2012 World Congress on In Vitro Biology
  • Place of Presentation: 米国
  • Invited
• [Presentation] 細胞内導入型RAGE阻害剤の開発 (2012)
  • Author(s): 8. Putoranto Endy Widya、村田 等、山本 健一、片岡 健、二見 淳一郎、山田 秀徳、阪口 政清、許 南浩
  • Organizer: 日本組織培養学会第85回大会
  • Place of Presentation: 京都