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Determination of cancer stem cells and evaluation for cancer immunotherapy against cancer stem cells

Research Project

Project/Area Number 24590498
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionNational Institute of Advanced Industrial Science and Technology

Principal Investigator

IKEHARA YUZURU  独立行政法人産業技術総合研究所, バイオメデイカル研究部門, 上級主任研究員 (10311440)

Co-Investigator(Renkei-kenkyūsha) YAMAGUCHI Takashi  独立行政法人産業技術総合研究所, バイオメデイカル研究部門, 契約職員 (60626563)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords膵臓がん / がん幹細胞 / 細胞分化 / 免疫治療 / 腺管構造の形成 / 幹細胞Sphere / 免疫応答 / T抗原エピトープ / マウスモデル / 三次元培養 / 不死化 / 幹細胞 / 腫瘍
Outline of Final Research Achievements

This study was conducted to increase knowledge about nature of stem cells in CK19+ pancreatic ductal epithelial cells. Established mouse pancreatic cancer and immortalized cell lines with CK19+ formed sphere structure (SS) and tubular structure (TS) in three dimension culture using collagen gels. We have demonstrated that there were differential types of stem cells in SS and TS, and presence of the cells determines SS and TS, respectively. Additionally, TGFβ and the signal transduction pathway was identified to promote from SS to TS conversion. Furthermore, immune reaction could control cancer cells growth of both SS and TS, while rejection of tumor cells was impaired by tolerance linked with CD4+CD25+regulatory T cells and monocyte with CD11b+ /F4/80+.
In conclusion, though there are different types of stem cells in pancreatic cancer, immune therapy is feasible to use for control over the differentiation status.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (39 results)

All 2015 2014 2013 2012 Other

All Journal Article (18 results) (of which Peer Reviewed: 16 results,  Open Access: 4 results) Presentation (18 results) (of which Invited: 9 results) Book (1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Comparison of intratumoral heterogeneity of HER2 expression between primary tumor and multiple organ metastases in gastric cancer: Clinicopathological study of three autopsy cases and one resected case2015

    • Author(s)
      Saito T, Kondo C, Shitara K, Ito Y, Saito N, Ikehara Y, Yatabe Y, Yamamichi K, Tanaka T, Nakanishi H
    • Journal Title

      Pathol Int

      Volume: 印刷中 Issue: 6 Pages: 309-317

    • DOI

      10.1111/pin.12290

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glycoproteomics approach for identifying Glycobiomarker candidate molecules for tissue type classification of non-small cell lung carcinoma.2014

    • Author(s)
      Hirao Y, Matsuzaki H, Iwaki J, Kuno A, Kaji H, Ohkura T, Togayachi A, Abe M, Nomura M, Noguchi M, Ikehara Y, Narimatsu H
    • Journal Title

      J Proteome Res

      Volume: 13(11) Issue: 11 Pages: 4705-4716

    • DOI

      10.1021/pr5006668

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A genetically engineered mouse model developing rapid progressive pancreatic ductal adenocarcinoma2014

    • Author(s)
      Yamaguchi T, Ikehara S, Nakanishi H, IkeharaY
    • Journal Title

      The Journal of Pathology

      Volume: 234(2) Issue: 2 Pages: 228-238

    • DOI

      10.1002/path.4402

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mice lacking α1,3-fucosyltransferase 9 exhibit modulation of in vivo immune responses against pathogens2014

    • Author(s)
      Kashiwazaki H, Kakizaki M, Ikehara Y, Togayachi A, Narimatsu H, Watanabe R
    • Journal Title

      Pathol Int

      Volume: 64(5) Issue: 5 Pages: 199-208

    • DOI

      10.1111/pin.12159

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and evaluation of a radioiodinated peptide probe targeting αvβ6 integrin for the detection of pancreatic ductal adenocarcinoma2014

    • Author(s)
      Ueda M, Fukushima T, Ogawa K, Kimura H, Ono M, Yamaguchi T, Ikehara Y, Saji H
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 445(3) Issue: 3 Pages: 661-666

    • DOI

      10.1016/j.bbrc.2014.02.086

    • NAID

      120005466666

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel glycobiomarker for ovarian cancer that detects clear cell carcinoma.2014

    • Author(s)
      Sogabe M, Nozaki H, Tanaka N, Kubota T, Kaji H, Kuno A, Togayachi A, Gotoh M, Nakanishi H, Nakanishi T, Mikami M, Suzuki N, Kiguchi K, Ikehara Y, Narimatsu H
    • Journal Title

      J Proteome Res

      Volume: 7 Issue: 3 Pages: 1624-1635

    • DOI

      10.1021/pr401109n

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 糖鎖情報から読み解く,生命活動と病理.2014

    • Author(s)
      池原 譲
    • Journal Title

      病理と臨床

      Volume: 32(6) Pages: 677-681

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 出血制御における従来手法と低温プラズマ法の比較.2014

    • Author(s)
      池原 譲
    • Journal Title

      静電気学会雑誌

      Volume: 38(4) Pages: 171-176

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Application of a Glycoproteomics-Based Biomarker Development Method: Alteration in Glycan Structure on Colony Stimulating Factor 1 Receptor as a Possible Glycobiomarker Candidate for Evaluation of Liver Cirrhosis.2014

    • Author(s)
      32) Ocho M, Togayachi A, Iio E, Kaji H, Kuno A, Sogabe M, Korenaga M, Gotoh M, Tanaka Y, Ikehara Y, Mizokami M, Narimatsu H.
    • Journal Title

      J Proteome Res.

      Volume: 13(3) Issue: 3 Pages: 1428-1437

    • DOI

      10.1021/pr400986t

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunoassay with single-walled carbon nanotubes as near-infrared fluoresent labels2013

    • Author(s)
      Yoko Iizumi, Toshiya Okazaki, Yuzuru Ikehara, Mutsuo Ogura, Shisuke Fukada, Masako Yudasaka
    • Journal Title

      Appl. Mater. & Interfaces

      Volume: 5 Issue: 16 Pages: 7665-7670

    • DOI

      10.1021/am401702q

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clgalt1-deficient mice exhibit thrombocytopenia due to abnormal terminal differentiation of megakaryocytes2013

    • Author(s)
      Kudo T, et al. (13人中8番目)
    • Journal Title

      Blood

      Volume: 122 Issue: 9 Pages: 1649-1657

    • DOI

      10.1182/blood-2012-12-471102

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Podocalyxin is a glycoprotein ligand of the human pluripotent stem cell-specific probe rBC2LCN2013

    • Author(s)
      Tateno H, Matsushima A, Hiemori K, Onuma Y, Ito Y, Hasehira K, Nishimura K,Ohtaka M, Takayasu S, Nakanishi M, Ikehara Y,Nakanishi M, Ohnuma K, Chan T,Toyoda M, Akutsu H, Umezawa A, Asashima M, Hirabayashi J.
    • Journal Title

      Stem Cells Transl Med.

      Volume: 2 Issue: 4 Pages: 265

    • DOI

      10.5966/sctm.2012-0154

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Glycoproteomics-based cancer marker discovery adopting dual enrichment with Wisteria floribunda agglutinin for high specific glyco-diagnosis of cholangiocarcinoma.2013

    • Author(s)
      Matsuda A, Kuno A, Matsuzaki H, Kawamoto T, Shinkai T, Nakanuma Y, Yamamoto M, Ohkohchi N, Ikehara Y, Shoda J, Hirabayashi J, Narimatsu H
    • Journal Title

      J Proteomics

      Volume: 85 Pages: 1-11

    • DOI

      10.1016/j.jprot.2013.04.017

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Different levels of Sialyl-Tn Antigen expressed on MUC16 in Patients With Endometriosis and Ovarian Cancer2012

    • Author(s)
      Akita K
    • Journal Title

      Int J Gynecol Cancer

      Volume: VOL.22(4) Issue: 4 Pages: 531-8

    • DOI

      10.1097/igc.0b013e3182473292

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] PCR Detection of Babesia ovata from Cattle Reared in Japan and Clinical Significance of Co-Infection with Theileria orientalis2012

    • Author(s)
      Sivakumar, T., Tagawa, M., Yoshinari, T., Ybanez, A. P., Igarashi, I., Ikehara, Y., Hata, H., Kondo, S., Matsumoto, K., Inokuma, H., and Yokoyama, N
    • Journal Title

      J. Clin. Microbiol

      Volume: 50 Issue: 6 Pages: 2111-3

    • DOI

      10.1128/jcm.00220-12

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment and characterization of novel gastric signet-ring cell and non signet-ring cell, poorly-differentiated adenocarcinoma cell lines with low and high malignant potential2012

    • Author(s)
      Murakami H, Nakanishi H, Tanaka H, Ito S, Misawa K, Ito Y, Ikehara Y, Kondo E, Kodera Y.
    • Journal Title

      Gastric Cancer

      Volume: (in press) Issue: 1 Pages: 74-83

    • DOI

      10.1007/s10120-012-0149-2

    • NAID

      40019557355

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] LecT-Hepa, a glyco-marker derived from multiple lectins, as a predictor of liver fibrosis in chronic hepatitis C patients2012

    • Author(s)
      Ito K, Kuno A, Ikehara Y, Sugiyama M, Saito H, Aoki Y, Matsui T, Imamura M, Korenaga M, Murata K, Masaki N, Tanaka Y, Hige S, Izumi N, Kurosaki M, Nishiguchi S, Sakamoto M, Kage M, Narimatsu H, Mizokami M
    • Journal Title

      Hepatology

      Volume: 56 Issue: 4 Pages: 1448-56

    • DOI

      10.1002/hep.25815

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of LecT-Hepa and FibroScan for assessment of liver fibrosis in hepatitis B virus infected patients with different ALT levels.2012

    • Author(s)
      DU Dongning
    • Journal Title

      Clin Chim Acta

      Volume: 413 Issue: 21-22 Pages: 21-22

    • DOI

      10.1016/j.cca.2012.07.005

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Feasibility and expanding roles of plasma coagulation technology to improve the prognosis of pancreatic cancer2015

    • Author(s)
      Yuzuru Ikehara
    • Organizer
      IWPCT2015
    • Place of Presentation
      名古屋大学
    • Year and Date
      2015-03-16 – 2015-03-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 糖鎖情報で読み解く、組織病理の世界2014

    • Author(s)
      池原 譲
    • Organizer
      第55回日本組織細胞化学会
    • Place of Presentation
      松本市公民館
    • Year and Date
      2014-09-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] グライコプロテオーム解析によるがんマーカーの開発2014

    • Author(s)
      池原 譲, 成松 久
    • Organizer
      第73回日本癌学会学術総会 JCA-JSP Joint Symposium.
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-26 – 2014-09-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] プラズマによる低侵襲止血が牽引する、すい臓がん克服のための診断治療技術の学際的研究開発2014

    • Author(s)
      池原 譲
    • Organizer
      新学術領域研究「プラズマ医療科学の創成」第3回公開シンポジウム
    • Place of Presentation
      名古屋大学
    • Year and Date
      2014-08-09
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] An application of low temperature plasma to achieve minimal invasive surgery2014

    • Author(s)
      Yuzuru Ikehara
    • Organizer
      5th International Conference on Plasma Medicine (ICPM5)
    • Place of Presentation
      Nara Prefectural New Public Hall
    • Year and Date
      2014-05-18 – 2014-05-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 3 次元培養法を用いたTGF-β による膵管上皮細胞の分化制御メカニズムの検討.2014

    • Author(s)
      山口高志, 池原早苗, 中西速夫, 池原譲
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 波長1.2-2 μm を捉える近赤外イメージングの開発とマクロ病理学への展開2014

    • Author(s)
      池原 譲
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] A clinical need for medical plasma equipment in line with progression of minimally invasive surgical procedure.2014

    • Author(s)
      Yuzuru Ikehara, Hajime Sakakita, Nobuyuki Shimizu, Sanae Ikehara, Hayao Nakanishi
    • Organizer
      8th International Conference on Reactive Plasmas/31st Symposium on Plasma Processing (ICRP8/SPP-31)Fukuoka
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] De novo 膵臓発がんモデルを用いたがん幹細胞と幹細胞ニッチの解析2013

    • Author(s)
      池原 譲、山口 高志、池原早苗
    • Organizer
      第102回 日本病理学会総会
    • Place of Presentation
      ロイトン札幌/さっぽろ芸文館
    • Related Report
      2013 Research-status Report
  • [Presentation] A genetically engineered mouse model of de novo pancreatic carcinogenesis2013

    • Author(s)
      Takashi Yamaguchi, Sanae K. Ikehara, Yuzuru Ikehara
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington, D.C
    • Related Report
      2013 Research-status Report
  • [Presentation] 硫酸化糖鎖の発現亢進によるホルモン不応答性前立腺癌増殖メカニズムと、その糖鎖バイオマーカーの可能性2013

    • Author(s)
      佐々木正雄、池原譲、佐藤慎哉、澤木弘道、平野和己、Toin H. van kuppevelt、中西速夫、西原祥子、成松久
    • Organizer
      第102回 日本病理学会総会
    • Place of Presentation
      ロイトン札幌/さっぽろ芸文館
    • Related Report
      2013 Research-status Report
  • [Presentation] 低侵襲性医療の実現に向けたプラズマ止血デバイスへの期待 -医療用マイルドプラズマによる創傷治癒の確立とプラズマ-組織細胞交互作用の解明2013

    • Author(s)
      池原 譲
    • Organizer
      文部科学省科学研究費新学術領域「プラズマ医療科学の創成」公開シンポジウム
    • Place of Presentation
      名古屋大学
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] プラズマによる低侵襲の出血制御および、プラズマ処置で生じる血液凝固物の創傷被覆材としての意義について.2013

    • Author(s)
      池原 譲
    • Organizer
      30th International Conference of Photopolymer Science and Technology (ICPST-30)
    • Place of Presentation
      千葉大学
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Meanings of glycobiological approaches to detect diseases

    • Author(s)
      Ikehara Y
    • Organizer
      Tsukuba Nanotechnology Symposium 2012
    • Place of Presentation
      Tsukuba, Japan
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Evaluation for ductal phenotype of mouse pancreatic ductal adenocarcinoma (PDAC) and the immortalized pancreatic ductal cells.

    • Author(s)
      Yamaguchi T., Ikehara S., Nakanishi H., Ikehara Y.
    • Organizer
      14th, Int. Natl. Cong. of Histochem. Cytochem.
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] 生物機能と疾患の理解を目指した糖鎖生物学研究

    • Author(s)
      池原 譲
    • Organizer
      第58回日本病理学会秋季特別総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] PathophysiologicalMeanings of PlasmaTreatment for Blood Bleeding and the Wound HealingProcess

    • Author(s)
      Ikehara Y* and Sakakita H.
    • Organizer
      Material Research Society 2012 Spring Meeting and Exhibition, 2012
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Plasma Physics and Its global Applications

    • Author(s)
      Sakakita H and Ikehara Y
    • Organizer
      Material Research Society 2012 Spring Meeting and Exhibition, 2012
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2012 Research-status Report
    • Invited
  • [Book] Mouse Models of Cancer. In: Glycoscience: Biology and Medicine. Edited by Taniguchi N, Endo T, and Hart GW.2014

    • Author(s)
      Ikehara Y, Yamaguchi T, Ikehara S.
    • Publisher
      Springer Reference.
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] 撮像システム及び撮像方法2013

    • Inventor(s)
      池原 譲、小倉 睦郎、牧野内 進
    • Industrial Property Rights Holder
      産業技術総合研究所、株式会社ニコン
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-113825
    • Filing Date
      2013-05-28
    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] 糖鎖アイソフォーム検出方法及び糖鎖アイソフォーム検出装置2013

    • Inventor(s)
      成松久、久野敦、池原譲、ほか4名
    • Industrial Property Rights Holder
      成松久、久野敦、池原譲、ほか4名
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-08-09
    • Related Report
      2013 Research-status Report
    • Overseas

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Published: 2013-05-31   Modified: 2019-07-29  

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