Development of chemoprevention and therapy against colorectal cancers by bone marrow mesenchymal stem cell transplantation

• Project/Area Number: 22590703
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: NAISHIRO Yasuyoshi 札幌医科大学, 医療人育成センター, 講師 (80347161)
• Co-Investigator(Kenkyū-buntansha): ARIMURA Yoshiaki 札幌医科大学, 医学部, 講師 (80305218) ; MOTOYA Masayo (HOSOKAWA Masayo) 札幌医科大学, オホーツク医療環境研究講座, 助教 (60468080)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 骨髄間葉系幹細胞(MSC) / 血管新生 / CXCL12 / 骨髄間葉系幹細胞（MSC） / 腫瘍血管新生 / activation-induced cytidine deaminase (AID) / CXCL12(4) / xenoraft / SDF-1/CXCR4 / VEGF / 血管周皮細胞

Research Abstract

MSC contributed to tumor engraftment via CXCL12/CXCR4 signaling and tumor progression through promoting angiogenesis. The mechanism of CXCL12 activation remains to be elucidated because it appears to be regulated by neither epigenetics nor miRNAs. These information concerning tumorigenic effects of MSC is necessity for clinical use of MSC therapy in the near future.

Research Products

• [Journal Article] Insulin-like growth factor receptor expression is associated with aggressive phenotypes and has therapeutic activity in biliary tract cancers. (2012)
  • Author(s): Ohashi H
  • Journal Title: Cancer Sci Volume: 103 Issue: 2 Pages: 252-261
  • DOI: 10.1111/j.1349-7006.2011.02138.x
  • Peer Reviewed
• [Journal Article] Eegenerative medicine for inflammatory bowel disease (2012)
  • Author(s): Yoshiaki Arimura
  • Journal Title: Inflammation and Regeneration Volume: 32 Pages: 61-66
• [Journal Article] Dynamics of claudins expression in colitis and colitis-associated cancer in rat (2011)
  • Author(s): Arimura Y, Nagaishi K, Hosokawa M
  • Journal Title: Methods Mol Biol Volume: 762 Pages: 409-425
• [Journal Article] The efficacy of IGF-I receptor monoclonal antibody against human gastrointestinal carcinomas is independent of k-ras mutation status (2011)
  • Author(s): Ii M, Li H, Adachi Y, Yamamoto H, Ohashi H, Taniguchi H, Arimura Y, Carbone DP, Imai K, Shinomura Y
  • Journal Title: Clin Cancer Res Volume: 17 Pages: 5048-5059
  • Peer Reviewed
• [Journal Article] Insulin-like growth factor-I receptor blockade reduces tumor angiogenesis and enhances the effects of bevacizumab for a human gastric cancer cell line (2011)
  • Author(s): Li H, Adachi Y, Yamamoto H, Min Y, Ohashi H, Ii M, Arimura Y, Endo T, Lee CT, Carbone DP, Imai K, Shinomura Y
  • Journal Title: MKN45. Cancer Volume: 117 Pages: 3135-3147
  • Peer Reviewed
• [Journal Article] Myogenic lineage differentiated mesenchymal stem cells enhance recovery from dextran sulfate sodium-induced colitis in the rat (2011)
  • Author(s): Tanaka H, Arimura Y, Yabana T, Goto A, Hosokawa M, Nagaishi K, Yamashita K, Yamamoto H, Sasaki Y, Fujimiya M, ImaiK, Shinomura Y
  • Journal Title: J Gastroenterol Volume: 46 Pages: 143-152
  • NAID: 10029027000
  • Peer Reviewed
• [Journal Article] Dynamics of claudins expression in colitis and colitis-associated cancerin rat (2011)
  • Author(s): Yoshiaki Arimura
  • Journal Title: Methods Mol Biol Volume: 762 Pages: 409-425
  • DOI: 10.1007/978-1-61779-185-7_29
  • ISBN: 9781617791840, 9781617791857
• [Journal Article] Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma (2010)
  • Author(s): Akutsu N, Yamamoto H, Sasaki S, Taniguchi H, Arimura Y, Imai K, Shinomura Y
  • Journal Title: World J Gastroenterol Volume: 16 Pages: 3521-3528
  • Peer Reviewed
• [Journal Article] Targeting for insulin-like growth factor-I receptor with short hairpin RNA for human digestive/gastrointestinal cancers (2010)
  • Author(s): Wang Y, Adachi Y, Imsumran A, Yamamoto H, Piao W, Li H, Ii M, Arimura Y, Park MY, Kim D, Lee CT, Carbone DP, Imai K, Shinomura Y
  • Journal Title: J Gastroenterol Volume: 45 Pages: 159-170
  • NAID: 10027214385
  • Peer Reviewed
• [Presentation] 骨髄間葉系幹細胞は azoxymethane による発癌のイニシエーションを一部解除する (2012)
  • Author(s): 那須野正尚,有村佳昭,渡邊秀平,中垣卓,永石歓和,苗代康可,山下健太郎,山本博幸,今井浩三,篠村恭久
  • Organizer: JDDW2012
  • Place of Presentation: 神戸
  • Year and Date: 2012-11-11
• [Presentation] Genetic Charasteristics of Japansese IBD (2012)
  • Author(s): Arimura Y
  • Organizer: Asian IBD Symposium
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2012-11-02
• [Presentation] 骨髄間葉系幹細胞は azoxymethane による発癌のイニシエーションを一部解除する (2012)
  • Author(s): 那須野正尚,有村佳昭,渡邊秀平,中垣卓,永石歓和,苗代康可,山下健太郎,山本博幸,今井浩三,篠村恭久
  • Organizer: 第49回日本消化器免疫学会総会
  • Place of Presentation: 鹿児島
  • Year and Date: 2012-07-06
• [Presentation] Pleiotropic Action of Gut Tropic Factors Derived from Conditioned Mesenchymal Stem Cells (2012)
  • Author(s): Nagaishi K, Watanabe S, Naishiro Y, Yamashita K, Arimura Y, Fujimiya M, Shinomura Y
  • Organizer: DDW2012
  • Place of Presentation: San Diego, US
  • Year and Date: 2012-05-19
• [Presentation] Pleiotropic Action of Gut Tropic Factors Derived from Conditioned Mesenchymal Stem Cells (2012)
  • Author(s): Nagaishi K, Watanabe S, Naishiro Y, Yamashita K, Arimura Y, Fujimiya M, Shinomura Y, Imai K
  • Organizer: 6th Japan-Korea IBD Symposium
  • Place of Presentation: Tokyo
  • Year and Date: 2012-01-28
• [Presentation] Genetic Charasteristics of Japansese IBD (2012)
  • Author(s): Arimura Y
  • Organizer: Asian IBD Symposium
  • Place of Presentation: Seoul
  • Invited
• [Presentation] Pleiotropic Action of Gut Tropic Factors Derived from Conditioned Mesenchymal Stem Cells (2012)
  • Author(s): Nagaishi K
  • Organizer: DDW2012
  • Place of Presentation: San Diego
• [Presentation] 骨髄間葉系幹細胞はazoxymethaneによる発癌のイニシエーションを一部解除する (2012)
  • Author(s): 那須野正尚
  • Organizer: 第49回日本消化器免疫学会総会
  • Place of Presentation: 鹿児島
• [Presentation] 骨髄間葉系幹細胞を用いた炎症性腸疾患の新規治療戦略 (2012)
  • Author(s): 永石歓和
  • Organizer: 第33回日本炎症・再生医学会
  • Place of Presentation: 福岡
• [Presentation] 骨髄間葉系幹細胞由来Gut Trophic Factor はラット実験腸炎の回復を促進する (2011)
  • Author(s): 渡邊秀平, 有村佳昭, 永石歓和, 那須野正尚,篠村恭久
  • Organizer: 第53回日本消化器病学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2011-10-20
• [Presentation] MSC 由来 Gut trophic factor のラット DSS 腸炎における役割 (2011)
  • Author(s): 永石歓和, 渡邊秀平, 那須野正尚, 苗代康可, 有村佳昭, 篠村恭久
  • Organizer: 第48回日本消化器免疫学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2011-07-21
• [Presentation] Reciprocal relation between MSC- dependent angiogenesis and VEGF expression in colorectal cancer (2011)
  • Author(s): Nagaishi K, Arimura Y, Nasuno M, Shinomura Y
  • Organizer: DDW2011
  • Place of Presentation: Chicago, US
  • Year and Date: 2011-05-10
• [Presentation] Reciprocal relation between MSC-dependent angiogenesis and VEGF expression in colorectal cancer (2011)
  • Author(s): Kanna Nagaishi
  • Organizer: DDW 2011
  • Place of Presentation: Chicago
  • Year and Date: 2011-05-10
• [Presentation] Reciprocal relation between tumor angiogenesis and MSC-dependent growth in colorectal cancer (2011)
  • Author(s): Nagaishi K, Arimura Y, Suzuki D, Ataka K, Shinomura Y, Fujimiya M
  • Organizer: 第116回日本解剖学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-30
• [Presentation] 骨髄間葉系幹細胞は大腸癌細胞の増殖を促進させる-腫瘍細胞の VEGF 発現と MSC 依存性増殖の関連 (2010)
  • Author(s): 中垣卓,有村佳昭,篠村恭久
  • Organizer: JDDW2010
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-14
• [Presentation] 骨髄間葉系幹細胞(MSC)は大腸癌細胞の生着を促進させる-腫瘍細胞のVEGF発現とMSC依存性増殖の関連- (2010)
  • Author(s): 中垣卓
  • Organizer: JDDW2010
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-14
• [Presentation] Reciprocal relation tumor angiogenesis with MSC-dependent growth in colorectal cancer cell lines xenograft (2010)
  • Author(s): Nasuno M, Arimura Y, Nakagaki S,Watanabe S, Nagaishi K, Naishiro Y,Imai K, Shinomura Y
  • Organizer: 5th Korea-Japan IBD Symposium
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2010-10-02
• [Presentation] Reciprocal relation tumor angiogenesis with MSC-dependent growth in colorectal cell lines xenograft (2010)
  • Author(s): Nasuno M
  • Organizer: The 5th Korea-Japan Inflammatory Bowel Disease Symposium
  • Place of Presentation: Seoul
  • Year and Date: 2010-10-02
• [Presentation] Enhancing mucosal reparative response in rat DSS colitis by mesenchymal stem cell therapy (2010)
  • Author(s): Tanaka H, Arimura Y, Yabana T, Goto A, Hosokawa M, Nagaishi K, Naishiro Y, Yamashita K, Yamamoto H, Murata M, Fujimiya M, Imai K, Shinomura Y
  • Organizer: 4th Korea-Japan IBD Symposium
  • Place of Presentation: Tokyo
  • Year and Date: 2010-01-23
• [Book] 炎症性腸疾患 病因解明と診断・治療の最新知見 ,炎症性腸疾患における発癌機序 (2012)
  • Author(s): 渡邊秀平,有村佳昭,今井浩三
  • Publisher: 日本臨床社
• [Book] 炎症性腸疾患の発癌機序 (2012)
  • Author(s): 渡邊秀平
  • Publisher: 日本臨床
• [Book] 炎症性腸疾患-病因解明と診断・治療の最新知見(炎症性腸疾患における発癌機序) (2012)
  • Author(s): 渡邊秀平
  • Publisher: 日本臨床社
• [Book] IBD(炎症性腸疾患)を究める,II.炎症性腸疾患の病因・病態組織修復・再生 (2011)
  • Author(s): 那須野正尚,有村佳昭,今井浩三
  • Publisher: メジカルビュー社
• [Book] IBD(炎症性腸疾患)を究める(II.炎症性腸疾患の病因・病態組織修復・再生) (2011)
  • Author(s): 那須野正尚
  • Publisher: メジカルビュー社
• [Book] 炎症性腸疾患(X 炎症性腸疾患における癌化機序) (2010)
  • Author(s): 那須野正尚
  • Publisher: 医学書院
• [Book] 大腸疾患NOW(腸炎関連発癌におけるMSCの役割) (2010)
  • Author(s): 有村佳昭
  • Publisher: 日本メディカルセンター
• [Book] 日本内科学会雑誌, II. 炎症性腸疾患の病理・病態生理3.遺伝的背景 (2009)
  • Author(s): 渡邊修平, 有村佳昭, 細川雅代, 田中浩紀, 篠村恭久, 今井浩三
  • Publisher: 日本内科学会
• [Book] 大腸疾患 NOW 2009,第二部 炎症性腸疾患をめぐる最近の話題 5.炎症と発癌における骨髄の役割 (2009)
  • Author(s): 中垣卓,細川雅代,有村佳昭
  • Publisher: 日本メディカルセンター
• [Remarks]
  • URL: http://web.sapmed.ac.jp/im1/SubPage/04_Kenkyu/Kaisetsu02.html
• [Remarks]
  • URL: http://web.sapmed.ac.jp/im1/SubPage/04_Kenkyu/Kaisetsu02.html
• [Patent(Industrial Property Rights)] 間葉系幹細胞(MSC)の培養上清を含む腸炎の予防・治療剤 (2011)
  • Inventor(s): 有村佳昭,永石歓和,渡邊秀平
  • Industrial Property Rights Holder: 札幌医科大学
  • Filing Date: 2011-07-13