New combinatorial approach to peritoneal dissemination of scirrhous gastric carcinoma based REIC/Dkk-3 gene therapy

• Project/Area Number: 21591699
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Okayama University
• Principal Investigator: KATAOKA Ken 岡山大学, 大学院・医歯薬学総合研究科, 講師 (10293317)
• Co-Investigator(Kenkyū-buntansha): SAKAGUCHI Masakiyo 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (70379840)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: REIC/Dkk-3 / Gene Therapy / Scirrhous Gastric Carcinoma / Peritoneal Dissemination / REIC / Dkk-3

Research Abstract

A single intraperitoneal injection of REIC/Dkk-3 adenovirus suppressed tumor dissemination and disease progression of scirrhous gastric carcinoma(SGC) in the mouse model. Immunomodulation by Ad-REIC led to recruitment of natural killer cells inside tumor nodules. We conclude that REIC/Dkk-3 gene therapy may be a potential tool in combinatorial approaches to achieve curative effects in SGC. We also demonstrated that PINK1, a key molecule for the mitochondrial protection system, was a new target molecule to sensitize resistant cancer cells to REIC/Dkk-3 gene therapy.

Research Products

• [Journal Article] S100A7 Promotes the Migration and Invasion of Osteosarcoma Cells via 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] Preclinical Safety and Efficacy of in Situ REIC/Dkk-3 Gene Therapy for Prostate Cancer (2012)
  • Author(s): Kawauchi K, Watanabe M, Kaku H, Huang P, Sasaki K, Sakaguchi M, Ochiai K, Huh NH, Nasu Y, Kumon H.
  • Journal Title: Acta Med Okayama Volume: 66 Pages: 7-16
  • NAID: 120003850603
  • Peer Reviewed
• [Journal Article] Partial sensitization of human bladder cancer cells to a gene-therapeutic adenovirus carrying REIC/Dkk-3 by downregulation of BRPK/PINK1 (2012)
  • Author(s): 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
• [Journal Article] A novel tumor suppressor, REIC/Dkk-3 gene identified by our in vitro transformation model of normal human fibroblasts works as a potent therapeutic anti-tumor agent (2011)
  • Author(s): Sakaguchi M, Huh NH, Namba M
  • Journal Title: Adv Exp Med Biol Volume: 720 Pages: 209-215
  • Peer Reviewed
• [Journal Article] Tumor suppressor REIC/Dkk-3 interacts with the dynein light chain, Tctex-1 (2011)
  • Author(s): Ochiai K, Watanabe M, Ueki H, Huang P, Fujii Y, Nasu Y, Noguchi H, Hirata T, Sakaguchi M, Huh NH, Kashiwakura Y, Kaku H, Kumon H
  • Journal Title: Biochem Biophys Res Commun Volume: 412 Pages: 391-395
  • Peer Reviewed
• [Journal Article] TIRAP, an adaptor protein for TLR2/4, transduces a signal from RAGE phosphorylated upon ligand binding (2011)
  • Author(s): Sakaguchi M, Murata H, Yamamoto KI, Ono T, Sakaguchi Y, Motoyama A, Hibino T, Kataoka K, Huh NH
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Journal Article] Intraperitoneal administration of an adenovirus vector carrying REIC/Dkk-3 gene suppresses peritoneal dissemination of scirrhous gastric carcinoma (2011)
  • Author(s): Than SS, Kataoka K, Sakaguchi M, Murata H, Abarzua F, Taketa C, Du G, Yashiro M, Yanagihara K, Nasu Y, Kumon H, Huh NH
  • Journal Title: Oncol Rep Volume: 25 Pages: 989-995
  • Peer Reviewed
• [Journal Article] Expression of REIC/Dkk-3 in normal and hyperproliferative epidermis (2011)
  • Author(s): Du G, Kataoka K, Sakaguchi M, Abarzua F, Than SS, Sonegawa H, Makino T, Shimizu T, Huh NH
  • Journal Title: Exp Dermtol Volume: 20 Pages: 273-277
  • Peer Reviewed
• [Journal Article] A New Cytosolic Pathway from a Parkinson's Disease-associated Kinase, BRPK/PINK1 : Activation of Akt via mTORC2 (2011)
  • Author(s): Murata H, Sakaguchi M, Jin Y, Sakaguchi Y, Futami J, Yamada H, Kataoka K, Huh NH
  • Journal Title: J Biol Chem Volume: 286 Pages: 7182-7189
  • Peer Reviewed
• [Journal Article] A novel tumor suppressor. REIC/Dkk-3 gene identified by our in vitro transformation model of normal human fibroblasts works as a potent therapeuticaoti-tumor agent (2011)
  • Author(s): Sakaguchi M
  • Journal Title: Adv Exp Med Biol Volume: 720 Pages: 209-215
  • DOI: 10.1007/978-1-4614-0254-1_17
  • ISBN: 9781461402534, 9781461402541
  • Peer Reviewed
• [Journal Article] TIRAP, an adaptor protein for TLR2/4, transduces a signal from RAGE phosphorylated upon ligand binding (2011)
  • Author(s): Sakaguchi M
  • Journal Title: PLoS One Volume: 6 Issue: 8 Pages: e23132-e23132
  • DOI: 10.1371/journal.pone.0023132
  • Peer Reviewed
• [Journal Article] Multiple functions of PINK1 at different intracellular locations : beyond neurodegenerative diseases (2011)
  • Author(s): Murata H
  • Journal Title: Cell Cycle Volume: 10 Issue: 10 Pages: 1518-1519
  • DOI: 10.4161/cc.10.10.15445
  • Peer Reviewed
• [Journal Article] Intraperitoneal administration of an adenovirus vector carrying REIC/Dkk-3 suppresses peritoneal dissemination of scirrhous gastric carcinoma (2011)
  • Author(s): Than SS
  • Journal Title: Oncol Rep Volume: 25 Issue: 4 Pages: 989-995
  • DOI: 10.3892/or.2011.1149
  • Peer Reviewed
• [Journal Article] Expression of REIC/Dkk-3 in normal and hyperproliferative epidermis. (2011)
  • Author(s): Du Gang
  • Journal Title: Experimental Dermatology Volume: 25 Pages: 273-277
  • Peer Reviewed
• [Journal Article] A New Cytosolic Pathway from a Parkinson's Disease-associated Kinase, BRPK/PINK1 : Activation of Aktvia mTORC2. (2011)
  • Author(s): Hitoshi Murata
  • Journal Title: Journal of Biological Chemistry Volume: 286 Pages: 7182-7189
  • Peer Reviewed
• [Journal Article] Internalization of REIC/Dkk-3 protein by induced pluripotent stem cell-derived embryoid bodies and extra-embryonic tissues (2010)
  • Author(s): Kataoka K, Sakaguchi M, Li KP, Taketa C, Yamamoto KI, Du G, Funahashi H, Murata H, Huh NH
  • Journal Title: Int J Mol Med Volume: 26 Pages: 853-859
  • Peer Reviewed
• [Journal Article] Application of a Thermo-Reversible Gelation Polymer, Mebiol Gel, for Stem Cell Culture and Regenerative Medicine (2010)
  • Author(s): Kataoka K, Huh NH
  • Journal Title: Journal of Stem cells and Regenerative medicine Volume: 6 Pages: 10-14
• [Journal Article] Down-regulation of Bip/Grp78 sensitizes resistant prostate cancer cells to gene-therapeutic overexpression of REIC/Dkk3 (2010)
  • Author(s): Tanimoto R, Sakaguchi M, Abarzua F, Kataoka K, Kurose K, Murata H, Nasu Y, Kumon H, Huh NH
  • Journal Title: Int J Cancer Volume: 126 Pages: 1562-1569
  • NAID: 120004724432
  • Peer Reviewed
• [Journal Article] Application of a Thermo-Reversible Gelation Polymer, Mebiol Gel, for Stem Cell Culture and Regenerative Medicine. (2010)
  • Author(s): Ken Kataoka
  • Journal Title: Journal of Stem Cells and Regenerative Medicine Volume: 6 Pages: 10-14
• [Journal Article] Down-regulation of Bip/Grp78 sensitizes resistant prostate cancer cells to gene-therapeutic overexpression of REIC/Dkk3 (2010)
  • Author(s): Ryuta Tanimoto
  • Journal Title: Int J of Cancer 126 Pages: 1562-1569
  • Peer Reviewed
• [Journal Article] Overexpression of REIC/Dkk-3 in normal fibroblasts suppresses tumor growth via induction of IL-7 (2009)
  • Author(s): Sakaguchi M, Kataoka K, Abarzua F, Tanimoto R, Watanabe M, Murata H, Than SS, Kurose K, Kashiwakura Y, Nasu Y, Kumon H, Huh NH
  • Journal Title: J Biol Chem Volume: 284 Pages: 14236-14244
  • Peer Reviewed
• [Journal Article] REIC/Dkk-3 stable transfection reduces the malignant phenotype of mouse prostate cancer RM9 cells (2009)
  • Author(s): Chen J, Watanabe M, Huang P, Sakaguchi M, Ochiai K, Nasu Y, Ouchida M, Huh NH, Shimizu K, Kashiwakura Y, Kaku H, Kumon H
  • Journal Title: Int JMol Med Volume: 24 Pages: 89-794
  • Peer Reviewed
• [Journal Article] Overexpression of REIC/Dkk-3 in normal fibroblasts suppresses tumor growth via induction of IL-7 (2009)
  • Author(s): Masakiyo Sakaguchi
  • Journal Title: J Biol Chem 284 Pages: 12436-12444
  • Peer Reviewed
• [Journal Article] REIC/Dkk-3 stable transfection reduces the malignant phenotype of mouse prostate cancer RM9 cells (2009)
  • Author(s): Jie Chen
  • Journal Title: Int J Mol Med 24 Pages: 789-794
  • Peer Reviewed
• [Journal Article] Expression pattern of REIC/Dkk-3 in mouse squamous epithelia
  • Author(s): Kataoka K, Du G, Maehara N, Murata H, Sakaguchi M, Huh N
  • Journal Title: Clin Exp Dermatol Volume: (In press)
• [Presentation] TIRAP is a critical transducer of RAGE-mediated inflammatory signaling (2011)
  • Author(s): 阪口政清
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05
• [Presentation] REIC/Dkk-3遺伝子治療～小胞体ストレスを介した多彩な抗腫瘍効果～ (2011)
  • Author(s): 片岡健
  • Organizer: 国立成育医療研究センター研究所特別セミナー
  • Place of Presentation: 東京
  • Year and Date: 2011-09-16
• [Presentation] PINK1 knockdown increases the apoptosis induced by adenovirus-mediated REIC/Dkk-3 overexpression on bladder cancer cells (2011)
  • Author(s): Jin Y
  • Organizer: 日本組織培養学会第84回大会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-28
• [Presentation] REIC/Dkk-3遺伝子治療~小胞体ストレスを介した多彩な抗腫瘍効果~ (2011)
  • Author(s): 片岡健
  • Organizer: 国立成育医療研究センター研究所特別セミナー
  • Place of Presentation: 東京
• [Presentation] The development of improved cultured epithelium usingβ3 cDNA-transduced keratinocytes to increase its take-rate (2011)
  • Author(s): Kubo M, Moriguchi M, Maehara M, Kataoka K, Huh NH, Inagawa K
  • Organizer: 17th International Society for Cellular Therapy Annual Meeting
  • Place of Presentation: オランダ
• [Presentation] 正常皮膚におけるREIC/Dkk-3の発現制御因子の検索 (2011)
  • Author(s): 前原奈都美、片岡健、杜剛、村田等、山本健一、阪口政清、許南浩
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Promotion of migration and invasion of osteosarcoma cells by S100A7 through RAGE (2011)
  • Author(s): Kataoka K, Sakaguchi M, Ono T, Morishita M, Yamamoto KI, Murata H, Huh NH
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] TIRAP is a critical transducer of RAGE-mediatedinflammatory signaling (2011)
  • Author(s): Sakaguchi M, Murata H, Yamamoto KI, Sakaguchi Y, Motoyama A, Hibino T, Kataoka K, Huh NH
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Mitochondrial malfunction by PINK1 knockdown augments apoptosis induced by adenovirus carrying REIC/Dkk-3 (2011)
  • Author(s): Murata H, Jin Y, Sakaguchi M, Kataoka K, Huh NH
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] REIC/Dkk-3の扁平上皮における発現とその制御因子の探索 (2011)
  • Author(s): 片岡健、阪口政清、杜剛、前原奈都美、村田等、許南浩
  • Organizer: 日本組織培養学会第84回大会
  • Place of Presentation: 東京
• [Presentation] PINK1 knockdown increases the apoptosis induced by adenovirus-mediated REIC/Dkk-3overexpression on bladder cancer cells (2011)
  • Author(s): Jin Y, Murata H, Kataoka K, Sakaguchi M, Huh NH
  • Organizer: 日本組織培養学会第84回大会
  • Place of Presentation: 東京
• [Presentation] BRPK/PINK1 promotes tumor progression through activation of mTORC2 pathway (2010)
  • Author(s): 村田等
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] TIRAP, an adaptor protein for TLR-2/-4, transduces a signal from RAGE phosphorylated upon ligand binding (2010)
  • Author(s): 阪口政清
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] Reduced expression of REIC/Dkk-3, a putative tumor suppressor gene, in hyperproliferative epidermis (2010)
  • Author(s): 杜剛
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] PINK1/BRPK inhibits apoptotic cell death and enahances cellular invasiveness through an activation of mTORC2 pathway (2010)
  • Author(s): Murata H, Sakaguchi M, Kataoka K, Huh NH
  • Organizer: The 16th International Charles Heidelberger Symposium on Cancer Research
  • Place of Presentation: ポルトガル
• [Presentation] BRPK/PINK1 promotes tumor progression through activation of mTORC2pathway (2010)
  • Author(s): Murata H, Sakaguchi M, Jin Y, Kataoka K, Huh NH
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] TIRAP, an adaptor protein for TLR-2/-4, transduces a signal from RAGE phosphorylated upon ligand binding(多機能受容体RAGEの下流信号伝達機構の解明) (2010)
  • Author(s): Sakaguchi M, Murata H, Yamamoto KI, Ono T, Sakaguchi Y, Motoyama A, Hibino T, Kataoka K, Huh NH
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] Intraperitoneal Administration of an Adenovirus Vector Carrying REIC/Dkk-3 Gene Suppresses Peritoneal Dissemination of Scirrhous Gastric Carcinoma Cells (2010)
  • Author(s): Kataoka K, Than SS, Sakaguchi M, Abarzua F, Taketa C, Yashiro M, Nasu Y, Kumon H, Huh NH
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] Reduced expression of REIC/Dkk-3, a putative tumor suppressor gene, in hyperproliferativeepidermis (2010)
  • Author(s): Du G, Kataoka K, Sakaguchi M, Makino T, Shimizu T, Huh NH
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] 分化誘導したマウスES細胞及びiPS細胞におけるCy3標識REIC/Dkk-3タンパク質のエンドサートーシスによる取り込み (2010)
  • Author(s): 片岡健、阪口政清、李坤鵬、杜剛、武田千佳、舟橋弘晃、村田等、許南浩
  • Organizer: 日本組織培養学会第83回大会
  • Place of Presentation: 岡山
• [Presentation] Effect of Adenovirus-mediated Overexpression of REIC/Dkk-3 on Scirrhous Gastric Carcinoma Cells (2010)
  • Author(s): Than SS, Kataoka K, Putranto EW, Murata H, Abarzua F, Taketa C, Yashiro M, Sakaguchi M, Huh NH
  • Organizer: 日本組織培養学会第83回大会
  • Place of Presentation: 岡山
• [Presentation] Current achievements and clinical application of stem cell research in Okayama University. International Symposium and Workshop for Stem Cell 〓 (2009)
  • Author(s): Ken Kataoka
  • Organizer: International Symposium and Workshop for Stem Cell Therapy
  • Place of Presentation: Makassar, Indonesia
  • Year and Date: 2009-10-31
• [Presentation] Promoter-based improvement of gene expression in cancer therapieutic adenovirus vector varrying REIC/Dkk-3 (2009)
  • Author(s): 阪口政清
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2009-10-03
• [Presentation] 幹細胞基礎研究の現状と未来～In vivo/in vitroにおける組織幹細胞研究～ (2009)
  • Author(s): 片岡健
  • Organizer: 日本組織培養学会第82回大会
  • Place of Presentation: 栃木県壬生町
  • Year and Date: 2009-05-18
• [Presentation] Current achievements and clinical application of stem cell research in Okayama University (2009)
  • Author(s): Kataoka K
  • Organizer: International Symposium and Workshop for Stem Cell Therapy
  • Place of Presentation: インドネシア
• [Presentation] 幹細胞基礎研究の現状と未来~ In vivo/in vitroにおける組織幹細胞研究~ (2009)
  • Author(s): 片岡健, 許南浩
  • Organizer: 本組織培養学会第82回大会シンポジウム
  • Place of Presentation: 栃木
• [Presentation] Impact of Bcl-xL deficiency in mouse keratinocytes on susceptibility to both UVB-and chemically-induced skin carcinogenesis (2009)
  • Author(s): Kim, DJ, Kataoka K, Sano S, Kiguchi K, DiGiovanni J
  • Organizer: 100th Annual Meeting of American Association for Cancer Research
  • Place of Presentation: 米国
• [Presentation] Intraperitoneal Normal human fibroblast mis-targetedly infected with adenovirus REIC have a tumor-suppressive abilitu in vivo (2009)
  • Author(s): Sakaguchi M, Kataoka K, Abarzua F, Tanimoto R, Watanabe M, Murata H, Than SS, Nasu Y, Kumon H, Huh NH
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] BRPK/PINK1のmTORC2経路活性化を介したがん浸潤への寄与 (2009)
  • Author(s): 村田等、阪口政清、片岡健、許南浩
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 超高効率発現ベクターの開発とがん遺伝子治療薬としてのREIC/Dkk-3アデノウィルスベクターへの応用 (2009)
  • Author(s): 阪口政清、片岡健、村田等、許南浩
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜