Regulation of heterogeneity of tumors from the viewpoint of cancer initiating cells

• Project/Area Number: 26460470
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Osaka University
• Principal Investigator: Morii Eiichi 大阪大学, 医学系研究科, 教授 (10283772)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 腫瘍幹細胞 / 多様性 / 制御因子 / 未熟性 / リンパ腫

Outline of Final Research Achievements

Cancer initiating cells are resistant to anti-tumor therapies. In this study, we showed that ALDH-hi cells, which are considered as cancer initiating cells, are regulated by Nodal, and that ALDH-hi cells expressed S100A4 strongly. S100A4 is related to proliferation and invasion ability of uterine endometrial carcinoma, and S100A4-hi cases possessed "MELF" pattern. In addition, arginine synthetic enzyme was also upregulated in ALDH-hi cells. This enzyme epigenetically controlled mTOR-complex member, DEPTOR. These results suggested that cancer initiating cells are controlled by various factors, which are related to yield of heterogenous populations of tumors.

Research Products

• [Journal Article] Heterogeneity of tumor cells in terms of cancer-initiating cells (2017)
  • Author(s): Morii E
  • Journal Title: Journal of Toxicologic Pathology Volume: 30 Issue: 1 Pages: 1-6
  • DOI: 10.1293/tox.2016-0056
  • NAID: 130005297231
  • ISSN: 0914-9198, 1881-915X
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Immunohistochemical analysis of the novel marginal-zone B-cell marker IRTA1 in malignant lymphoma. (2017)
  • Author(s): Ikeda JI, Kohara M, Tsuruta Y, Nojima S, Tahara S, Ohshima K, Kurashige M, Wada N, Morii E.
  • Journal Title: Hum Pathol Volume: 59 Pages: 70-79
  • DOI: 10.1016/j.humpath.2016.09.011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Podocalyxin influences malignant potential by controlling epithelial-mesenchymal transition in lung adenocarcinoma. (2017)
  • Author(s): Kusumoto H, Shintani Y, Kanzaki R, Kawamura T, Funaki S, Minami M, Nagatomo I, Morii E, Okumura M.
  • Journal Title: Cancer Sci. Volume: 108 Issue: 3 Pages: 528-535
  • DOI: 10.1111/cas.13142
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Argininosuccinate Synthase 1-Deficiency Enhances the Cell Sensitivity to Arginine through Decreased DEPTOR Expression in Endometrial Cancer. (2017)
  • Author(s): Ohshima K, Nojima S, Tahara S, Kurashige M, Hori Y, Hagiwara K, Okuzaki D, Oki S, Wada N, Ikeda JI, Kanai Y, Morii E.
  • Journal Title: Sci Rep. Volume: 7 Pages: 45504-45504
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ID1 upregulation and FoxO3a downregulation by Epstein-Barr virus-encoded LMP1 in Hodgkin's lymphoma. (2016)
  • Author(s): Ikeda JI, Wada N, Nojima S, Tahara S, Tsuruta Y, Oya K, Morii E.
  • Journal Title: Mol Clin Oncol. Volume: 5 Pages: 562-566
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] S100A4 accelerates the proliferation and invasion of endometrioid carcinoma and is associated with the ‘MELF’ pattern. (2016)
  • Author(s): Tahara S, Nojima S, Ohshima K, Hori Y, Kurashige M, Wada N, Ikeda J, Morii E.
  • Journal Title: Cancer Sci Volume: 109 Issue: 9 Pages: 1345-1352
  • DOI: 10.1111/cas.12999
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Requirement of CXCL12-CXCR7 signaling for CD20- CD138- double-negative population in lymphoplasmacytic lymphoma. (2016)
  • Author(s): Wada N, Ikeda J, Nojima S, Tahara S, Ohshima K, Okuzaki D, Morii E.
  • Journal Title: Lab Invest. Volume: 96 Issue: 5 Pages: 517-525
  • DOI: 10.1038/labinvest.2016.28
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Similar protein expression profiles of ovarian and endometrial high-grade serous carcinomas. (2016)
  • Author(s): Hiramatsu K, Yoshino K, Serada S, Yoshihara K, Hori Y, Fujimoto M, Matsuzaki S, Egawa-Takata T, Kobayashi E, Ueda Y, Morii E, Enomoto T, Naka T, Kimura T.
  • Journal Title: Br J Cancer. Volume: 114 Pages: 554-61
  • Peer Reviewed
• [Journal Article] New guidelines for HER2 pathological diagnostics in gastric cancer. (2016)
  • Author(s): Wada R, Hirabayashi K, Ohike N, Morii E.
  • Journal Title: Pathol Int. Volume: 66 Issue: 2 Pages: 57-62
  • DOI: 10.1111/pin.12390
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Poorly differentiated hepatocellular carcinoma accompanied by anti-Hu antibody-positive paraneoplastic peripheral neuropathy. (2015)
  • Author(s): Matsui T, Hori Y, Nagano H, Eguchi H, Marubashi S, Wada H, Wada N, Ikeda J, Sakamoto M, Morii E.
  • Journal Title: Pathol Int. Volume: 65 Issue: 7 Pages: 388-392
  • DOI: 10.1111/pin.12304
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Atypical glomus tumor arising in the liver: a case report. (2015)
  • Author(s): Hirose K, Matsui T, Nagano H, Eguchi H, Marubashi S, Wada H, Morii E.
  • Journal Title: Diagn Pathol. Volume: 10 Pages: 112-112
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Characterization of subpopulation lacking both B-cell and plasma cell markers in Waldenstrom macroglobulinemia cell line. (2014)
  • Author(s): Wada N, Zhan M, Hori Y, Honma K, Ikeda J, Morii E.
  • Journal Title: Lab Invest. Volume: 94 Issue: 1 Pages: 79-88
  • DOI: 10.1038/labinvest.2013.129
  • Peer Reviewed
• [Journal Article] Roles of histamine on the expression of aldehyde dehydrogenase 1 in endometrioid adenocarcinoma cell line. (2014)
  • Author(s): Wang Y, Jiang Y, Ikeda J, Tian T, Sato A, Ohtsu H, Morii E .
  • Journal Title: Cancer Medicine Volume: 3 Issue: 5 Pages: 1126-1135
  • DOI: 10.1002/cam4.296
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] S100A4は子宮内膜癌の増殖と浸潤を促進する (2016)
  • Author(s): 田原 紳一郎, 池田 純一郎, 森井 英一
  • Organizer: 日本癌学会
  • Place of Presentation: パシフィコ横浜
• [Presentation] A novel techonology amd molecular cytology (2016)
  • Author(s): Eiichi Morii
  • Organizer: International Cytology Conference
  • Place of Presentation: パシフィコ横浜
  • Int'l Joint Research / Invited
• [Presentation] 腫瘍幹細胞とニッチ (2015)
  • Author(s): 森井英一
  • Organizer: 第１６回日本毒性病理学会教育セミナー
  • Place of Presentation: 大阪市立大学
  • Year and Date: 2015-11-04
  • Invited
• [Presentation] Heterogeneity of Cancer Cells from the Viewpoint of Cancer Initiating Cells (2015)
  • Author(s): Eiichi Morii
  • Organizer: The 21th Histopathology Conference Osaka-Shanghai-Melbourne
  • Place of Presentation: 大阪市立大学
  • Year and Date: 2015-11-01
  • Int'l Joint Research / Invited
• [Presentation] 小児血管腫血管奇形の病理 (2015)
  • Author(s): 森井英一
  • Organizer: 第３１回日本小児外科秋季シンポジウム
  • Place of Presentation: 熊本市
  • Year and Date: 2015-10-31
  • Invited
• [Presentation] 腫瘍の多様性を組織でみる (2015)
  • Author(s): 森井英一
  • Organizer: 第５６回日本組織細胞化学会
  • Place of Presentation: 関西医科大学
  • Year and Date: 2015-10-04
  • Invited
• [Presentation] 子宮類内膜腺癌細胞株のアルデヒド脱水素酵素活性におけるヒスタミンの役割 (2014)
  • Author(s): 池田純一郎、森井英一
  • 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: 2014-04-26
• [Presentation] ワルデンストロームマクログロブリン血症におけるCD20(-)CD138(-)細胞の意義 (2014)
  • Author(s): 和田直樹、森井英一
  • 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
• [Remarks] 腫瘍におけるアミノ酸代謝酵素の局在の違い
  • URL: http://www.med.osaka-u.ac.jp/introduction/research/pathology/histopathology
• [Remarks] 腫瘍における免疫染色とin situ hybridizationの同時染色
  • URL: http://www.med.osaka-u.ac.jp/introduction/research/pathology/histopathology