To determine the epigenetic regulatory mechanism of cancer stem cells by cell surface molecules.

2011 Fiscal Year Final Research Report

• Project/Area Number: 22650223
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Carcinogenesis
• Research Institution: The University of Tokyo
• Principal Investigator: MORIMOTO Chikao 東京大学, 医科学研究所, 教授 (30119028)
• Co-Investigator(Kenkyū-buntansha): HOSONO Osamu 東京大学, 医科学研究所, 講師 (50190210) ; IWATA Satoshi 東京大学, 医科学研究所, 特任講師 (00396871)
• Project Period (FY): 2010 – 2011
• Keywords: がん幹細胞 / エピジェネティックス / B-ALL / 悪性中皮腫 / CD9 / CD24 / CD26 / USP22

Research Abstract

In the current study, we performed more detailed analysis of CD9 function for the cancer stem cell properties of B-ALL. In patient samples, CD9 was expressed in the most cases of B-ALL cells with significant correlation of CD34-expression. Knockdown of CD9 remarkably reduced the leukemogenic potential and affected the expression and tyrosine phosphorylation of Src family protein and reduced the expression of histone-deubiquitinase USP22. In malignant mesothelioma our results showed that CD24 and CD26 differentially regulated the cancer stem cell potentials of MM and also CD26 expression closely correlated with expression of USP22. These results suggest that CD24, CD9 and CD26 could be the promising target for CSC-oriented therapy.

Research Products

• [Journal Article] Characterization of cancer stem cell properties of CD24 and CD26-positive human malignant mesothelioma cells (2012)
  • Author(s): Yamazaki H, Naito M, Ghani FI, Dang NH, Iwata S, Morimoto C
  • Journal Title: Biochem Biophys Res Commun Volume: 419 Pages: 529-36
  • DOI: DOI:10.1016/j.bbrc.2012.02.054
• [Journal Article] CD26 overexpression is associated with prolonged survival and enhanced chemosensitivity in malignant pleural mesothelioma (2012)
  • Author(s): Aoe K, Amatya VJ, Fujimoto N, Ohnuma K, Hosono O, Hiraki A, Fujii M, Yamada T, Dang NH, Takeshima Y, Inai K, Kishimoto T, Morimoto C
  • Journal Title: Clin Cancer Res. Volume: 18 Pages: 1447-1456
  • DOI: DOI:10.1158/1078-0432.CCR-11-1990
• [Journal Article] Overexpression of CD26/DPPIV in mesothelioma tissue and mesothelioma cell lines (2011)
  • Author(s): Amatya VJ, Takeshima Y, Kushitani K, Yamada T, Morimoto C, Inai K
  • Journal Title: Oncol Rep Volume: 26 Pages: 1369-1375
  • DOI: DOI:10.3892/or.2011.1449
• [Journal Article] Regulation of cancer stem cell properties by CD9 in human B-acute lymphoblastic leukemia (2011)
  • Author(s): Yamazaki H, Wilson Xu C, Naito M, Nishida H, Okamoto T, Ghani FI, Iwata S, Inukai T, Sugita K, Morimoto C
  • Journal Title: Biochem Biophys Res Commun Volume: 409 Pages: 14-21
  • DOI: DOI:10.1016/j.bbrc.2011.04.098
• [Journal Article] Diet-Induced Adipose Tissue Inflammation and Liver Steatosis Are Prevented by DPP-4 Inhibition in Diabetic Mice (2011)
  • Author(s): Shirakawa J, Fujii H, Ohnuma K, Sato K, Ito Y, Kaji M, Sakamoto E, Koganei M, Sasaki H, Nagashima Y, Amo K, Aoki K, Morimoto C, Takeda E, Terauchi Y
  • Journal Title: Diabetes Volume: 60 Pages: 1246-57
  • DOI: DOI:10.2337/db10-1338
• [Journal Article] Crosstalk between glucocorticoid receptor and nutritional sensor mTOR in skeletal muscle (2011)
  • Author(s): Shimizu N, Yoshikawa N, Ito N, Maruyama T, Suzuki Y, Takeda S, Nakae J, Tagata Y, Nishitani S, Takehana K, Sano M, Fukuda K, Suematsu M, Morimoto C, Tanaka H
  • Journal Title: Cell Metab Volume: 13 Pages: 170-82
  • DOI: DOI:10.1016/j.cmet.2011.01.001
• [Journal Article] Mechanisms of confluence-dependent expression of CD26 in colon cancer cell lines (2011)
  • Author(s): Abe M, Havre PA, Urasaki Y, Ohnuma K, Morimoto C, Dang LH, Dang NH
  • Journal Title: BMC Cancer Volume: 11 : 51
  • DOI: DOI:10.1186/1471-2407-11-51
• [Journal Article] Identification of cancer stem cell markers in human malignant mesothelioma cells (2011)
  • Author(s): Ghani FI, Yamazaki H, Iwata S, Okamoto T, Aoe K, Okabe K, Mimura Y, Fujimoto N, Kishimoto T, Yamada T, Xu CW, Morimoto C
  • Journal Title: Biochem Biophys Res Commun Volume: 404 Pages: 735-42
• [Journal Article] Targeted therapy by monoclonal antibodies (2010)
  • Author(s): Ohnuma K, Morimoto C
  • Journal Title: Nippon Rinsho Volume: 68 Pages: 1841-7
• [Journal Article] Inhibition of dipeptidyl peptidase 4 regulates microvascular endothelial growth induced by inflammatory cytokines (2010)
  • Author(s): Takasawa W, Ohnuma K, Hatano R, Endo Y, Dang NH, Morimoto C
  • Journal Title: Biochem Biophys Res Commun Volume: 401 Pages: 7-12
  • DOI: DOI:10.1016/j.bbrc.2010.08.112
• [Journal Article] Optimal stimulation for CD70 induction on human monocyte-derived dendritic cells and the importance of CD70 in naive CD4(+) T-cell differentiation (2010)
  • Author(s): Arimoto-Miyamoto K, Kadowaki N, Kitawaki T, Iwata S, Morimoto C, Uchiyama T
  • Journal Title: Immunology Volume: 130 Pages: 137-49
  • DOI: DOI:10.1111/j.1365-2567.2010.03220.x
• [Presentation] The Current Status of Drug Development and the Role of Clinical Trial Centers in Japan (2011)
  • Author(s): Morimoto C
  • Organizer: International Symposium of Clinical Trial
  • Place of Presentation: Jeju, Korea
  • Year and Date: 2011-10-07
• [Book] Adv Clin Chem (2011)
  • Author(s): Ohnuma K, Hosono O, Dang NH, Morimoto C
  • Total Pages: 51-84
  • Publisher: Dipeptidyl peptidase in autoimmune pathophysiology
• [Book] Stem cell property for T-cell malignancy. T-Cell Malignancies : Recent Developments and Novel Therapeutic Approaches (2010)
  • Author(s): Yamazaki H and Morimoto C
  • Total Pages: 197-202
  • Publisher: Edited by Dang NH
• [Book] The role of CD26 in T-cell biology and T-cell malignancies. T-Cell Malignancies : Recent Developments and Novel Therapeutic Approaches
  • Author(s): Havre PA, Dang LH, Abe M, Urasaki Y, Ohnuma K, Morimoto C, Dang NH
  • Total Pages: 37-54
  • Publisher: Edited by Dang NH