Studies on digestive cancer metastasis using mouse models

2008 Fiscal Year Final Research Report

• Project/Area Number: 19209010
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: TAKETO Makoto Kyoto University, 医学研究科, 教授 (70281714)
• Co-Investigator(Kenkyū-buntansha): AOKI Masahiro 京都大学, 医学研究科, 准教授 (60362464) ; KITAMURA Takanori 京都大学, 医学研究科, 助教 (10378622) ; SONOSHITA Masahiro 京都大学, 医学研究科, 助教 (80511857) ; MIYOSHI Hiroyuki (30362479)
• Project Period (FY): 2007 – 2008
• Keywords: 分子腫瘍学

Research Abstract

Aes (amino-terminal enhancer of split)が大腸癌の血行性転移を抑制すること、その機序として、Aes がNotch シグナル抑制を介して癌細胞の血管内侵入を阻害することを、マウスモデルを用いて明らかにした.AES の発現消失はヒト大腸癌の肝転移とも相関していた.また、ケモカイン受容体CXCR3 の阻害薬はメラノーマのリンパ節転移を抑制し、CXCR3がリンパ節転移の治療標的となる可能性が示された.

Research Products

• [Journal Article] Matrix metalloproteinase 7 is required for tumor formation, but dispensable for invasion and fibrosis in SMAD4 -deficient intestinal adenocarcinomas (2009)
  • Author(s): Kitamura, T., Biyajima, K., Aoki, M., Oshima, M., Taketo, M. M.
  • Journal Title: Lab Invest 89 Pages: 98-105
  • Peer Reviewed
• [Journal Article] Role of bone marrow-derived cells in colon cancer : lessons from mouse model studies (2009)
  • Author(s): Taketo MM.
  • Journal Title: J Gastroenterol 44 Pages: 93-102
  • Peer Reviewed
• [Journal Article] Mouse models of colon cancer (2009)
  • Author(s): Taketo, M. M., Edelmann, W.
  • Journal Title: Gastroenterology(Review) 136 Pages: 780 -98
  • Peer Reviewed
• [Journal Article] Stromal fibroblasts activated by tumor cells promote angiogenesis in mouse gastric cancer (2008)
  • Author(s): Guo, X., Oshima, H., Kitmura, T., Taketo, M.M., Oshima, M
  • Journal Title: J. Biol. Chem 283 Pages: 19864-19871
  • Peer Reviewed
• [Journal Article] Activated macrophages promote Wnt signalling through tumour necrosis factor -alpha in gastric tumour cells (2008)
  • Author(s): Oguma, K., Oshima, H., Aoki, M., Uchio, R., Naka, K., Nakamura, S., Hirao, A., Saya, H., Taketo, M.M., Oshima, M
  • Journal Title: EMBO J 27 Pages: 1671-1681
  • Peer Reviewed
• [Journal Article] Inhibition of the mTORC1 pathway suppresses intestinal polyp formation and reduces mortality in Apc^<Δ716> mice. Proc (2008)
  • Author(s): Fujishita, T., Aoki, K., Lane, H.A., Aoki, M., Taketo, M.M.
  • Journal Title: Natl. Acad. Sci. USA 105 Pages: 13544-13549
  • Peer Reviewed
• [Journal Article] Tissue-specific transgenic, conditional knockout and knock-in mice of genes in the canonical Wnt signaling pathway (2008)
  • Author(s): Aoki, K., Taketo, M. M.
  • Journal Title: Methods Mol Biol 468 Pages: 307-31
  • Peer Reviewed
• [Journal Article] Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes (2007)
  • Author(s): Kawada, K., Hosogi, H., Sonoshita, M., Sakashita, H., Manabe, T., Shimahara, Y., Sakai, Y., Takabayashi, A., Oshima, M., Taketo, M.M
  • Journal Title: Oncogene 26 Pages: 4679-4688
  • Peer Reviewed
• [Presentation] Mouse Models for Colon Cancer Invasion and Metastasis (2009)
  • Author(s): Taketo, M. M.
  • Organizer: AACR Meeting "Mouse Models of Cancer
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 20090112-15
• [Presentation] Suppression of colon cancer metastasis by Aes through inhibition of Notch signaling (2008)
  • Author(s): Taketo, M. M.
  • Organizer: Notch and Cancer Meeting
  • Place of Presentation: Athens, Greece
  • Year and Date: 20081005-08
• [Presentation] Keynote Lecture "What animal models tell us about gastrointestinal carcinogenesis (2008)
  • Author(s): Taketo, M. M.
  • Organizer: Fifth International Society of Gastroenterological Carcinogenesis Conference
  • Place of Presentation: Oxford, UK
  • Year and Date: 20080831-0901
• [Presentation] Novel Mechanism of Colon Cancer Invasion : Role of Bone -Marrow Derived Cells in cis-Apc^+/- Smad4^+/- mice (2008)
  • Author(s): Taketo, M. M.
  • Organizer: Joint Metastasis Society-AACR Conference on Metastasis
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 20080803-07
• [Presentation] Roles of Smoothened (Smo), the major signal transducer of the hedgehog pathway, in the development of intestinal tumors (2008)
  • Author(s): Sumimasa Arimura, Masahiro Aoki, and Makoto Mark Taketo
  • Organizer: 2008 AACR Annual Meeting
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2008-04-15
• [Remarks]
  • URL: http://www4.mfour.med.kyoto-u.ac.jp/
• [Patent(Industrial Property Rights)] CXCR3 阻害剤を含有する医薬組成物 (2009)
  • Inventor(s): 武藤誠, 河田健二
  • Industrial Property Rights Holder: 国立大学法人京都大学
  • Industrial Property Number: 特許, 2005219322
  • Acquisition Date: 2009-01-08
  • Overseas