Role of bone-marrow derived mesenchymal stem cells in growth and metastasis of colon cancer.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590813
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hiroshima University
• Principal Investigator: KITADAI Yasuhiko 広島大学, 大学院・医歯薬学総合研究科, 准教授 (10304437)
• Co-Investigator(Renkei-kenkyūsha): SHINAGAWA Kei 広島大学, 病院, 医科診療医 (50623609)
• Project Period (FY): 2009 – 2011
• Keywords: 下部消化管学(小腸、大腸) / 骨髄由来間葉系幹細胞 / 間質 / 癌転移 / 分子標的治療

Research Abstract

In an orthotopic nude mice model of colon cancer, mesenchymal stem cells(MSCs) traveled to tumor stroma, where they differentiated into carcinoma-associated fibroblast(CAF)-like cells. The KM12SM+ MSC xenograft enhanced cell proliferation and angiogenesis and inhibited tumor cell apoptosis. When tumor-bearing animals were treated with imatinib, there was no significant increase in primary tumor volume or total volume of liver metastases, despite the KM12SM+ MSC xenograft, and survival in the mixed-cell group was prolonged by imatinib treatment. Moreover, the ability of MSCs to migrate to tumor stroma was impaired, and the number of MSCs surviving in the tumor microenvironment was significantly decreased. Our data suggest that blockade of PDGF signaling pathways influences the interaction between bone marrow-derived MSCs and tumor cells in the tumor microenvironment and, hence, inhibits the progressive growth of colon cancer.

Research Products

• [Journal Article] Stroma-directed molecular targeted therapyin gastric cancer (2011)
  • Author(s): Kitadai, Y., Kodama, M., Shinagawa, K.
  • Journal Title: Cancers Volume: 3 Pages: 4245-4057
  • Peer Reviewed
• [Journal Article] Anti-stromal therapy with imatinib inhibits growth and metastasis of gastric carcinoma in an orthotopic nude mouse model (2011)
  • Author(s): Sumida, T., Kitadai, Y., Shinagawa, K., Tanaka, M., Kodama, M., Ohnishi, M., Ohara, E., Tanaka, S., Yasui, W., Chayama, K.
  • Journal Title: Int J Cancer Volume: 128 Pages: 2050-2062
  • Peer Reviewed
• [Journal Article] Angiogenesis and lymphangiogenesis of gastric cancer (2010)
  • Author(s): Kitadai, Y.
  • Journal Title: J. Oncol. 2010 Volume: Article ID 468725
  • Peer Reviewed
• [Journal Article] Expression of platelet-derivedgrowth factor(PDGF)-B and PDGF-receptor beta is associated with lymphatic metastasis in human gastric carcinoma (2010)
  • Author(s): Kodama, M., Kitadai, Y., Sumida, T., Ohnishi, M., Ohara, E., Tanaka, M., Shinagawa, K., Tanaka, S., Yasui, W., Chayama, K.
  • Journal Title: Cancer Sci Volume: 101 Pages: 1984-1989
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cells enhance growthand metastasis of colon cancer (2010)
  • Author(s): Shinagawa, K., Kitadai, Y., Tanaka, M., Sumida, T., Kodama, M., Higashi, Y., Tanaka, S., Yasui, W., Chayama, K.
  • Journal Title: Int J Cancer Volume: 127 Pages: 2323-2333
  • Peer Reviewed
• [Journal Article] Potential rolefor vascular endothelial growth factor-D asan autocrine factor for human gastric carcinoma cells (2010)
  • Author(s): Tanaka, M., Kitadai, Y., Kodama, M., Shinagawa, K. Sumida, T., Tanaka, S., Oue, N., Yasui, W., Chayama, K.
  • Journal Title: Cancer Sci Volume: 101 Pages: 2121-2127
  • Peer Reviewed
• [Journal Article] Cancer-stromal cell interaction and tumor angiogenesis in gastric cancer (2009)
  • Author(s): Kitadai, Y.
  • Journal Title: Cancer Microenviron. Epub
  • Peer Reviewed
• [Presentation] Blockade ofPDGFR signaling impairs the tumorpromoting effect of bone marrow-derivedmesenchymal stem cells in colon cancer (2011)
  • Author(s): Shinagawa, K., Kitadai, Y., Ohnishi, M., Ohara, E., Tanaka, M., Sumida, T., Tanaka, S., Yasui, W., Chayama, K.
  • Organizer: 102st Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: Orland, FL, USA,
  • Year and Date: 20110400
• [Presentation] Blockade of PDGFR signaling with imatinib inhibits lymph node metastasis ofgastric carcinoma in an orthotopic nudemouse model (2011)
  • Author(s): Kitadai, Y., Kodama, M., Sumida, T., Shinagawa, K., Tanaka, S., Chayama, K.
  • Organizer: Montreal International Symposium on Angiogenesis and Metastasis (MISAM)
  • Place of Presentation: Montreal, Quebec, Canada
  • Year and Date: 2011-06-15
• [Presentation] Blockade of PDGFRsignaling impairs the tumor promotingeffect of bone marrow-derivedmesenchymal stem cells in colon cancer (2010)
  • Author(s): Kitadai, Y., Shinagawa, K., Tanaka, M., Sumida, T., Kodama, M., Tanaka, S., Yasui, W., Chayama, K.
  • Organizer: Joint Metastasis Research Society-AAC Rconference
  • Place of Presentation: Philadelphia, PA, USA
  • Year and Date: 20100400
• [Presentation] Significance of mesenchymal stem cells in growth and metastasis of colon cancer (2010)
  • Author(s): Shinagawa, K., Kitadai, Y., Tanaka, M., Sumida, T., Kodama, M., Tanaka, S., Yasui, W., Chayama, K.
  • Organizer: 101st Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: Washington D.C., USA
  • Year and Date: 2010-04-19
• [Book] Enhancedgrowth and metastasis of colon cancer : Roleof mesenchymal stem cells. Stem Cells andCancer Stem Cells (2012)
  • Author(s): Kitadai, Y., Shinagawa, K
  • Publisher: TherapeuticApplications in Disease and Injury
• [Book] Regulation of lymphangiogenesis in human gastric cancer (2011)
  • Author(s): Kitadai, Y., Kodama, M
  • Publisher: Trends in Cancer Research, Volume