Analysis of intercellular adhesion molecules expressed in cancer stem cells of a Tax-transgenic mouse ATL model

2012 Fiscal Year Final Research Report

• Project/Area Number: 23790454
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: SUZUKI Tadaki 国立感染症研究所, 感染病理部, 研究員 (30527180)
• Project Period (FY): 2011 – 2012
• Keywords: 疾患モデル動物 / 成人T 細胞白血病モデルマウス

Research Abstract

Adult T-cell leukemia (ATL) is a T-cell malignancy caused by human T lymphotropic virus type I. The HTLV-I transactivator, Tax, initiates ATL-like disease (mATL) both in Tax transgenic mice (Tax-Tg). Recently, the candidates CSCs of mATL were identified in splenic lymphomatous cells (SLCs). The candidate CSCs could consistently regenerate the original lymphoma, suggesting that the eradication of cancer stem cells will be necessary to improve the outcome of treatment for mATL. In this study, a proteomic approach was used to identify proteins differentially present in CSCs of mATL. The CSCs of mATL were analyzed by liquid chromatography tandem mass spectrometry to compare protein profiles in CSCs and no-CSCs. This comparative proteomic analysis revealed that expression of one membrane protein was increased in CSCs, which might become a new target of antibody-based therapy. Flowcytometry validated expression of the membrane protein. Taken together, the data presented provide a significant new protein-level insight into the biology of cancer stem cells of mATL, a key population of cells that are also involved in mATL development.

Research Products

• [Journal Article] HTLV-1 と白血病・リンパ腫 (2013)
  • Author(s): 鈴木 忠樹, 長谷川 秀樹
  • Journal Title: 病理と臨床 Volume: 31(2) Pages: 146-150
• [Journal Article] Spi-B is critical for plasmacytoid dendritic cell function and development. (2012)
  • Author(s): Sasaki I, Hoshino K, Sugiyama T, Yamazaki C, Yano T, Iizuka A, Hemmi H, Tanaka T, Saito M, Sugiyama M, Fukuda Y, Ohta T, Sato K, Ainai A, Suzuki T, Hasegawa H, Toyama-Sorimachi N, Kohara H, Nagasawa T, Kaisho T
  • Journal Title: Blood Volume: 6 Pages: 4733-43
  • DOI: doi:10.1182/blood-2012-06-436527
  • Peer Reviewed
• [Presentation] Comparative proteomic analysis of cancer stem cells in a Tax-transgenic (Tax-Tg) mouse model of adult T-cell leukemia/lymphoma (2011)
  • Author(s): Tadaki Suzuki, Akiko Okayama, Takahiro Tsuji, Akihide Ryo, Hisashi Hirano, Tetsutaro Sata, William W. Hall, Hideki Hasegawa
  • Organizer: The 15th International Conference on Human Retrovirology: HTLV and Related Retroviruses
  • Place of Presentation: Belgium
  • Year and Date: 20110604-08