Identification and characterization of human gastric cancer stem cells

• Project/Area Number: 22501005
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: FUKAMACHI Hiroshi 東京医科歯科大学, 大学院・医歯学総合研究科, 講師 (70134450)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: がん細胞の特性 / 幹細胞 / 胃がん / がん幹細胞 / 造腫瘍性 / FACS / ヌードマウス / 無血清培養 / sphere / 細胞表面抗原 / Xenograft / spheroids / ヒト

Research Abstract

We established xenograft lines where human gastric tumor tissues maintain their differentiation and tumorigenesis. Using these lines, we identified a marker which was specifically expressed by gastric cancer stem cells. We also confirmed that the marker was expressed by cancer stem cells which were obtained from newly-dissected gastric cancers. Moreover, we established serum-free culture system where gastric cancer stem cells proliferate to form spheres, structures specific to stem cells. These sphere-forming cells expressed the antigen and were highly tumorigenic. We are now examining the mechanism how their tumorigenicity is controlled.

Research Products

• [Journal Article] Synergistic tumour suppressor activity of E-cadherin and p53 in a conditional mouse model for metastatic diffuse-type gastric cancer (2012)
  • Author(s): Shimada S, et al.
  • Journal Title: Gut Volume: 61 Issue: 3 Pages: 344-353
  • DOI: 10.1136/gutjnl-2011-300050
  • Peer Reviewed
• [Journal Article] CD133 is a marker of gland-forming cells in gastric tumors and Sox17 is involved in its regulation (2011)
  • Author(s): Fukamachi, H., Shimada, S., Ito, K., Ito, Y., and Yuasa Y.
  • Journal Title: Cancer Sci. Volume: 102 Pages: 1313-1321
  • NAID: 10029295180
  • Peer Reviewed
• [Journal Article] Loss of E-cadherin in mouse gastric epithelial cells induces signet ring-like cells, possible precursor lesion of diffuse gastric cancer (2011)
  • Author(s): Mimata. A., Fukamachi, H., Eishi, Y., and Yuasa, Y.
  • Journal Title: Cancer Sci. Volume: 102 Pages: 942-950
  • NAID: 10029293200
  • Peer Reviewed
• [Journal Article] Loss of Runx3 is a key event in inducing precancerous state of the stomach (2011)
  • Author(s): Ito, K., Chuang, L. S. H., Ito, T., Chang, T. L., Fukamachi, H., Salto. Tellez, M., and Ito, Y.
  • Journal Title: Gastroenterology Volume: 140 Pages: 1536-1546
  • Peer Reviewed
• [Journal Article] Loss of E-cadherin in mouse gastric epithelial cells induces signet ring-like cells, possible precursor lesion of diffuse gastric cancer (2011)
  • Author(s): Mimata. A., Fukamachi, H., et al
  • Journal Title: Cancer Sci Volume: 102 Issue: 5 Pages: 942-950
  • DOI: 10.1111/j.1349-7006.2011.01890.x
  • NAID: 10029293200
  • Peer Reviewed
• [Journal Article] CD133 is a marker of gland-forming cells in gastric tumors and Sox17 is involved in its regulation (2011)
  • Author(s): Fukamachi, H., et al
  • Journal Title: Cancer Sci Volume: 102 Issue: 7 Pages: 1313-1321
  • DOI: 10.1111/j.1349-7006.2011.01947.x
  • NAID: 10029295180
  • Peer Reviewed
• [Journal Article] Loss of E-cadherin in mouse gastric epithelial cells induces signet ring-like cells, possible precursor lesion of diffuse gastric cancer (2011)
  • Author(s): Mimata, A., et al.
  • Journal Title: Cancer Science Volume: 102 印刷中
  • Peer Reviewed
• [Journal Article] CD133 is a marker of gland-forming cells in gastric tumors and Sox17 is involved in its regulation. (2011)
  • Author(s): Fukamachi.H., et al.
  • Journal Title: Cancer Science Volume: 102 印刷中
  • NAID: 10029295180
  • Peer Reviewed
• [Journal Article] Claudin-1 has tumor suppressive activity and is a direct target of RUNX3 in gastric epithelial cells (2010)
  • Author(s): Chang, T. L., Ito, K., Ko, T. K., Liu, Q., Salto-Tellez, M., Yeoh, K. G., Fukamachi, H., and Ito, Y.
  • Journal Title: Gastroenterology Volume: 138 Pages: 255-265
  • NAID: 120006984679
  • Peer Reviewed
• [Journal Article] miR-212 is down-regulated and suppresses methyl-CpG-binding protein MeCP2 in human gastric cancer (2010)
  • Author(s): Wada, R., Akiyama, Y., Hashimoto, Y., Fukamachi, H., and Yuasa, Y.
  • Journal Title: Int. J. Cancer Volume: 127 Pages: 1106-1114
  • Peer Reviewed
• [Journal Article] Claudin-1 has tumor suppressive activity and is a direct target of RUNX3 in gastric epithelial cells. (2010)
  • Author(s): Chang, T.L., et al
  • Journal Title: Gastroenterology Volume: 138 Pages: 225-265
  • Peer Reviewed
• [Journal Article] miR-212 is down-regulated and suppresses methyl-CpG-binding protein MeCP2 in human gastric cancer. (2010)
  • Author(s): Wada, R, et al.
  • Journal Title: Int.J.Cancer Volume: 127 Pages: 1106-1114
  • Peer Reviewed
• [Presentation] Identification and characterization of human gastric tumor-initiating cells (2011)
  • Author(s): Fukamachi, H.
  • Organizer: Seoul Pathology Forum
  • Place of Presentation: Seoul National University Hospital, Seoul, Korea
  • Year and Date: 2011-12-16
• [Presentation] Epigenetic changes in gastric cancer stem cells (2011)
  • Author(s): Fukamachi, H.
  • Organizer: NSFC A3 Foresight Program 2011 Workshop-Epigenetic Signatures in Gastric Carcinogenesis
  • Place of Presentation: Xi' an, China
  • Year and Date: 2011-10-09
• [Presentation] Epigenetic changes in gastric cancer stem cells (2011)
  • Author(s): Fukamachi, H.
  • Organizer: NSFC A3 Foresight Program 2011 Workshop- Epigenetic Signatures in Gastric Carcinogenesis
  • Place of Presentation: Xijing Hospital, Xi'an, China
  • Year and Date: 2011-10-09
• [Presentation] Identification and characterization of human gastric tumor-initiating cells (2011)
  • Author(s): Fukamachi, H., Shimada, S., Yuasa, Y.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] Runx3 protects gastric cepithelial cells against EMT and Lgr5-expressing tumorigenic subpopulation (2011)
  • Author(s): Ito, Y., Ito, K., Fukamachi, H.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] Identification and characterization of human gastric tumor-initiating cells (2011)
  • Author(s): Fukamachi, H., Shimada, S., Yuasa, Y.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-04
• [Presentation] Synergistic tumor suppressor activity of E-cadherin and p53 in a conditional mouse model for diffuse-type gastric cancer (2011)
  • Author(s): Shimada, S., Mimata, A., Akiyama, Y., Fukamachi, H., Yuasa Y.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] Runx3 protects gastric cepithelial cells against EMT and Lgr5-expressing tumorigenic subpopulation (2011)
  • Author(s): Ito, Y., Ito, K., Fukamachi, H.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-03
• [Presentation] Synergistic tumor suppressor activity of E-cadherin and p53 in a conditional mouse model for diffuse-type gastric cancer (2011)
  • Author(s): Shimada, S., et al
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-03
• [Presentation] Identification of tumor-initiating cells in human gastric cancers (2011)
  • Author(s): Fukamachi, H., Seol, H., Shimada, S., Jang, S., Yuasa, Y.
  • Organizer: IGCC 2011-9th International Gastric Cancer Congress
  • Place of Presentation: Coex Center, Seoul, Korea
  • Year and Date: 2011-04-22
• [Presentation] Mouse model of diffuse-type gastric cancer by conditional inactivation of E-cadherin and p53 (2011)
  • Author(s): Shimada, S., Mimata, A., Mogushi, K., Akiyama, Y., Fukamachi, H., Jonkers, J., Tanaka, H., Eishi, Y., Yuasa, Y.
  • Organizer: IGCC 2011-9th International Gastric Cancer Congress
  • Place of Presentation: Coex Center, Seoul, Korea
  • Year and Date: 2011-04-21
• [Presentation] Identification of tumor-initiating cells in human gastric cancers (2011)
  • Author(s): Fukamachi, H., et al
  • Organizer: IGCC 2011-9^<th> Int.Gastric Cancer Congress
  • Place of Presentation: Coex Center, Seoul, Korea
  • Year and Date: 2011-04-21
• [Presentation] Mouse model of diffuse-type gastric cancer by conditional inactivation of E-cadherin and p53 (2011)
  • Author(s): Shimada, S., et al
  • Organizer: IGCC 2011-9^<th> Int.Gastric Cancer Congress
  • Place of Presentation: Coex Center, Seoul, Korea
  • Year and Date: 2011-04-21
• [Presentation] Identification of tumor-initiating cells in human gastric cancers (2011)
  • Author(s): Fukamachi, H., Seol, H. S., Shimada, S., Jang, S. J., Yuasa, Y.
  • Organizer: 10th Japan-Korea Joint Symposium on Cancer and Ageing Research
  • Place of Presentation: Japanese Foundation for Cancer Research, Tokyo, Japan
  • Year and Date: 2011-02-14
• [Presentation] Synergistic tumor suppressor activity of E-cadherin and p53 in a conditional mouse model for diffuse-type gastric cancer (2011)
  • Author(s): Shimada, S., Mimata, A., Mogushi, K., Akiyama, Y., Fukamachi, H., Tanaka, H., Eishi, Y., Yuasa, Y.
  • Organizer: 10th Japan-Korea Joint Symposium on Cancer and Ageing Research
  • Place of Presentation: Japanese Foundation for Cancer Research, Tokyo, Japan
  • Year and Date: 2011-02-14
• [Presentation] Identification of tumor-initiating cells in human gastric cancers (2010)
  • Author(s): Fukamachi, H., Shimada, S., Seol, H. S., Jang, S. J., Yuasa, Y.
  • Organizer: NSFC A3 Foresight Program 2010 Seminar : Epigenetic Signatures in Gastric Carcinogenesis
  • Place of Presentation: Beijing, China
  • Year and Date: 2010-10-18
• [Presentation] Synergistic tumor suppressor activity of E-cadherin and p53 in a conditional mouse model for metastatic diffuse-type gastric cancer (2010)
  • Author(s): Shimada, S. Mimata, A., Akiyama, Y., Fukamachi, H., Eishi, Y., Yuasa, Y.
  • Organizer: NSFC A3 Foresight Program 2010 Seminar : Epigenetic Signatures in Gastric Carcinogenesis
  • Place of Presentation: Beijing, China
  • Year and Date: 2010-10-18
• [Presentation] Loss of E-cadherin in parietal cells affects gastric epithelial cell polarity, growth and differentiation, resulting in a pre-malignant condition in mice (2010)
  • Author(s): Mimata, A., Fukamachi, H., Eishi, Y., Yuasa, Y.
  • Organizer: NSFC A3 Foresight Program 2010 Seminar : Epigenetic Signatures in Gastric Carcinogenesis
  • Place of Presentation: Beijing, China
  • Year and Date: 2010-10-18
• [Presentation] Identification of tumor-initiating cells in human gastric cancers. (2010)
  • Author(s): Fukamachi.H., et al.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] Precancerous changes are induced in E-cadherin KO mouse stomachs (2010)
  • Author(s): Mimata, A., Fukamachi, H., Yuasa, Y.
  • 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] Identification of tumor-initiating cells in human gastric cancers (2010)
  • Author(s): Fukamachi, H., Shimada, S., Yuasa, Y.
  • 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] RLTNX3(R122C)does not attenuate oncogenic Wnt in gastric epithelial cells (2010)
  • Author(s): Ito, K., et al.
  • 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] Invasive diffuse gastric cancers develop in E-cadherin/p53 conditional double knockout mice (2010)
  • Author(s): Shimada, S., Mimata, A., Akiyama, Y., Fukamachi, H., Yuasa Y.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] RUNX3(R122C) does not attenuate oncogenic Wnt in gastric epithelial cells (2010)
  • Author(s): Ito, K., Fukamachi, H., Ito, Y.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] Invasive diffuse gastric cancers develop in E-cadherin/p53 conditional double knockout mice. (2010)
  • Author(s): Shimada, S., et al.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] Identification of tumor-initiating cells in human gastric cancers (2010)
  • Author(s): Fukamachi, H., Shimada, S., Seol, H. S., Funasaka, C., Jang, S. J., Yuasa, Y.
  • Organizer: The 5th Asian Epigenomics Meeting & A3 Symposium 2010
  • Place of Presentation: Jeju、Korea
  • Year and Date: 2010-06-21
• [Book] ヒトの分子遺伝学 (2011)
  • Author(s): 深町博史
  • Publisher: 細胞と細胞間情報伝達機構、発生の仕組み
• [Book] ヒトの分子遺伝学第4版 (2011)
  • Author(s): 深町博史, 他
  • Total Pages: 878
  • Publisher: メディカル・サイエンス・インターナショナル
• [Book] 生物の事典 (2010)
  • Author(s): 深町博史、阿形清和、浅川満彦、安部由美子、安藤元一、石原勝敏、一石昭彦、伊野良夫、井上弘一、井上裕介、今井一郎、岩崎俊晴、上田均、大串隆之、大島範子、大西純一、加藤泰建、金子康子、河内美樹、熊澤慶伯、桑野博行、小池文人、鯉淵典之、小柴共一、小林哲也、坂井貴文、佐藤利幸、白山義久、末光隆志、菅原敬、須永伊知郎、相馬早苗、平良眞規、竹内隆、武田洋幸、多田正純、舘鄰、舘野正樹、田中修、田中秀逸、田中実、土屋公幸、戸田年総、戸田任重、二階堂昌孝、野本茂樹、乗越浩司、橋口康之、畠山晋、林進、平野弘道、前島正義、町田
  • Total Pages: 560
  • Publisher: 朝倉書店
• [Book] 生物学辞典 (2010)
  • Author(s): 深町博史
  • Total Pages: 1634
  • Publisher: 東京化学同人
• [Remarks]
  • URL: http://www.tmd.ac.jp/grad/monc/index.html