Identification of specific cancer stem cell markers for diagnosis

• Project/Area Number: 24650632
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Tumor diagnosis
• Research Institution: The University of Tokyo
• Principal Investigator: IMAI Kohzoh 東京大学, 医科学研究所, 特任教授 (60117603)
• Co-Investigator(Kenkyū-buntansha): TANIGUCHI Hiroaki 東京大学, 医科学研究所, 特任准教授 (90563289)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 腫瘍マーカー / がん幹細胞 / がん / 遺伝子 / 臨床 / 癌

Research Abstract

We started our project to identfy specific cancer stem cell markers for diagnosis. ES cell markers and phenotypic markers of cancer proliferation are used to identify CSCs. We already have reported that PRDM14 expression is enhanced in clinical BC cases. We also show that KLF2 repression has an important role in EZH2 oncogenesis in breast and prostate cancers. PRDM14 and KLF2 are known to be important for ES cells maintainance. Accoding to our planning, we collected sphere-forming cells or SP fractions using a cell sorter in order to obtain cancer cells with stemness phenotypes from clinical cancer tissues. After that, we applied samples from those cells and normal control cells for a next generation sequencer to obtain the candidate genes. We could obtain several candidate genes for specific cancer stem cell markers and already have finished functional analysis for them. Now, we proceed to analyse clinical breast and pancreatic cancer tissues for specific cancer stem cell markers.

Research Products

• [Journal Article] Mesenchymal stem cells cancel azoxymethane-induced tumor initiation (2014)
  • Author(s): Nasuno M, Arimura Y, Nagaishi K, Isshiki H, Onodera K, Nakagaki S, Watanabe S, Idogawa M, Yamashita K, Naishiro Y, Adachi Y, Suzuki H, Fujimiya M, Imai K, Shinomura Y
  • Journal Title: Stem Cells Volume: 32 Issue: 4 Pages: 913-925
  • DOI: 10.1002/stem.1594
  • Peer Reviewed / Open Access
• [Journal Article] The effect of IGF-I receptor blockade for human esophageal squamous cell carcinoma and adenocarcinoma (2014)
  • Author(s): Adachi Y, Ohashi H, Imsumran A, Yamamoto H, Matsunaga Y, Taniguchi H, Nosho K, Suzuki H, Sasaki Y, Arimura Y, Carbone DP, Imai K, Shinomura Y
  • Journal Title: Tumour Biol Volume: 35 Issue: 2 Pages: 973-985
  • DOI: 10.1007/s13277-013-1131-2
  • Peer Reviewed
• [Journal Article] Conditioned mesenchymal stem cells produce pleiotropic gut trophic factors (2014)
  • Author(s): Watanabe S, Arimura Y, Nagaishi K, Isshiki H, Onodera K, Nasuno M, Yamashita K, Idogawa M, Naishiro Y, Murata M, Adachi Y, Fujimiya M, Imai K, Shinomura Y
  • Journal Title: J Gastroenterol Volume: 49 Issue: 2 Pages: 270-282
  • DOI: 10.1007/s00535-013-0901-3
  • Peer Reviewed
• [Journal Article] Aberrant methylation of microRNA-34b/c is a predictive marker of metachronous gastric cancer risk (2013)
  • Author(s): Suzuki R, Yamamoto E, Nojima M, Maruyama R, Yamano HO, Yoshikawa K, Kimura T, Harada T, Ashida M, Niinuma T, Sato A, Nosho K, Yamamoto H, Kai M, Sugai T, Imai K, Suzuki H, Shinomura Y
  • Journal Title: J Gastroenterol Volume: (Epub ahead of print)
• [Journal Article] Methylation of a panel of microRNA genes is a novel biomarker for detection of bladder cancer (2013)
  • Author(s): Shimizu T, Suzuki H, Nojima M, Kitamura H, Yamamoto E, Maruyama R, Ashida M, Hatahira T, Kai M, Masumori N, Tokino T, Imai K, Tsukamoto T, Toyota M
  • Journal Title: Eur Urol Volume: 63 Issue: 6 Pages: 1091-1100
  • DOI: 10.1016/j.eururo.2012.11.030
  • Peer Reviewed
• [Journal Article] Association between genomic alterations and metastatic behavior of colorectal cancer identified by array-based comparative genomic hybridization. (2013)
  • Author(s): Sawada T, Yamamoto E, Suzuki H
  • Journal Title: Genes Chromosomes Cancer Volume: 52(2) Issue: 2 Pages: 140-9
  • DOI: 10.1002/gcc.22013
  • Peer Reviewed
• [Journal Article] Cancer detection by ubiquitin carboxyl-terminal esterase L1 methylation in pancreatobiliary fluids (2013)
  • Author(s): Kato N, Yamamoto H, Adachi Y, Ohashi H, Taniguchi H, Suzuki H, Nakazawa M, Kaneto H, Sasaki S, Imai K, Shinomura Y
  • Journal Title: World J Gastroenterol Volume: 19(11) Issue: 11 Pages: 1718-1727
  • DOI: 10.3748/wjg.v19.i11.1718
  • Peer Reviewed
• [Journal Article] Characteristics of Japanese inflammatory bowel disease susceptibility loci (2013)
  • Author(s): Arimura Y, Isshiki H, Onodera K, Nagaishi K, Yamashita K, Sonoda T, Matsumoto T, Takahashi A, Takazoe M, Yamazaki K, Kubo M, Fujimiya M, Imai K, Shinomura Y
  • Journal Title: J Gastroenterol Aug 13 Volume: Epub ahead of print
• [Journal Article] Aberrant methylation of microRNA-34b/c is a predictive marker of metachronous gastric cancer risk. (2013)
  • Author(s): Suzuki R, Yamamoto E, Nojima M, Maruyama R, Yamano HO, Yoshikawa K, Kimura T, Harada T, Ashida M, Niinuma T, Sato A, Nosho K, Yamamoto H, Kai M, Sugai T, Imai K, Suzuki H, Shinomura Y.
  • Journal Title: J Gastroenterol Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Characteristics of Japanese inflammatory bowel disease susceptibility loci. (2013)
  • Author(s): Arimura Y, Isshiki H, Onodera K, Nagaishi K, Yamashita K, Sonoda T, Matsumoto T, Takahashi A, Takazoe M, Yamazaki K, Kubo M, Fujimiya M, Imai K, Shinomura Y.
  • Journal Title: J Gastroenterol Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Emerging links between epigenetic alterations and dysregulation of noncoding RNAs in cancer (2012)
  • Author(s): Maruyama R, Suzuki H, Yamamoto E, Imai K, Shinomura Y
  • Journal Title: Tumour Biol Volume: 33 Issue: 2 Pages: 277-85
  • DOI: 10.1007/s13277-011-0308-9
  • Peer Reviewed
• [Journal Article] Molecular Dissection of Premalignant Colorectal Lesions Reveals Early Onset of the CpG Island Methylator Phenotype. (2012)
  • Author(s): Yamamoto E, Suzuki H, Yamano HO
  • Journal Title: Am J Pathol Volume: 181(5) Issue: 5 Pages: 1847-61
  • DOI: 10.1016/j.ajpath.2012.08.007
  • Peer Reviewed
• [Journal Article] Model of translational cancer research in multiple myeloma (2012)
  • Author(s): Yasui H, Ishida T, Maruyama R, Nojima M, Ikeda H, Suzuki H, Hayashi T, Shinomura Y, Imai K
  • Journal Title: Cancer Sci Volume: 103 Issue: 11 Pages: 1907-1912
  • DOI: 10.1111/j.1349-7006.2012.02384.x
  • Peer Reviewed
• [Journal Article] Aberrant Methylation of RASGRF1 Is Associated with an Epigenetic Field Defect and Increased Risk of Gastric Cancer. (2012)
  • Author(s): Takamaru H, Yamamoto E, Suzuki H.
  • Journal Title: Cancer Prev Res (Phila) Volume: 5(10) Issue: 10 Pages: 2012-2012
  • DOI: 10.1158/1940-6207.capr-12-0056
  • Peer Reviewed
• [Journal Article] Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors (2012)
  • Author(s): Takeshi Niinuma
  • Journal Title: Cancer research Volume: 72 Issue: 5 Pages: 1126-36
  • DOI: 10.1158/0008-5472.can-11-1803
  • Peer Reviewed
• [Journal Article] Silencing of the Kruppel-like factor 2 by the histone methyltransferase EZH2 in human cancer (2012)
  • Author(s): Taniguchi H, Jacinto F.V., Villanueva A, Fernandez AF, Yamamoto H, Carmona F.J, Puertas S, Marquez VE, Shinomura Y, Imai K, and Esteller M
  • Journal Title: Oncogene Volume: 31 Issue: 15 Pages: 1988-1994
  • DOI: 10.1038/onc.2011.387
  • Peer Reviewed
• [Journal Article] A DNA methylation fingerprint of 1628 human samples (2011)
  • Author(s): Fernandez AF, Assenov Y, Martin-Subero JI, Balint B, Siebert R, Taniguchi H, Yamamoto H, Hidalgo M, Tan AC, Galm O, Ferrer I, Sanchez-Cespedes M, Villanueva A, Carmona J, Sanchez-Mut JV, Berdasco M, Moreno V, Capella G, Monk D, Ballestar E, Ropero S, Martinez R, Sanchez-Carbayo M, Prosper F, Agirre X, Fraga MF, Grana O, Perez-Jurado L, Mora J, Puig S, Prat J, Badimon L, Puca AA, Meltzer SJ, Lengauer T, Bridgewater J, Bock C, Esteller M
  • Journal Title: Genome Res Volume: 22(2) Issue: 2 Pages: 407-19
  • DOI: 10.1101/gr.119867.110
  • Peer Reviewed
• [Presentation] ヒストンメチル化酵素分子の発現亢進による乳癌細胞の悪性形質獲得 (2013)
  • Author(s): 谷口博昭、山本博幸、今井浩三
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-10-04
• [Presentation] ヒストンメチル化酵素分子の発現亢進による乳癌細胞の悪性形質獲得とその臨床応用 (2013)
  • Author(s): 谷口博昭、山本博幸、伊東文生、今井浩三
  • Organizer: 第33回日本分子腫瘍マーカー研究会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-10-02
• [Presentation] ヒストンメチル化酵素分子の発現亢進による乳癌細胞の悪性形質獲得 (2013)
  • Author(s): 谷口博昭、山本博幸、越川直彦、清木元治、今井浩三
  • Organizer: 第22回日本がん転移学会学術集会
  • Place of Presentation: ホテルブエナビスタ松本(長野県松本市)
  • Year and Date: 2013-07-11
• [Presentation] ヒストンメチル化酵素分子の発現亢進による乳癌細胞の悪性形質獲得 (2013)
  • Author(s): 谷口博昭、山本博幸、越川直彦、清木元治、今井浩三
  • Organizer: 第22回日本がん転移学会学術集会
  • Place of Presentation: 松本市
• [Remarks] 東京大学医科学研究所附属病院抗体・ワクチンセンター
  • URL: http://www.nctimsut.org/
• [Remarks] 東京大学医科学研究所附属病院 抗体・ワクチンセンター
  • URL: http://www.nctimsut.org/