Analysis of transformation processes by using the "two-hit leukemogenesis model"

• Project/Area Number: 25290047
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: Sugamura Kazuo 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), その他部局等, その他 (20117360)
• Co-Investigator(Kenkyū-buntansha): SASAKI OSAMU 宮城県立がんセンター研究所, 発がん制御研究部, 特任研究員 (40538055) ; KAZUNORI YAMAGUCHI 宮城県立がんセンター研究所, 発がん制御研究部, 上席主任研究員 (80373215) ; 井根 省二 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), その他部局等, 研究員 (80573683)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 白血病 / 免疫不全マウス / ATL / HTLV-1 / 成人T細胞白血病 / シグナル伝達

Outline of Final Research Achievements

To identify a molecule which plays a role in the initiation or malignant transformation of leukemia, we established leukemia stem cell-like cells from leukemia-derived cell lines which show high tumorigenicity in NOG mice. Micro array analysis and RNA-seq analysis revealed the aberrant expression patterns of CADM1 and CA9 genes, both of which encode cell surface proteins. Further analysis on these molecules indicated unveiled molecular mechanisms underlying tumorigenicity of leukemia cells. Our results help understanding malignant transformation of leukemia cells and suggest new possible targets for the leukemia intervention.

Research Products

• [Journal Article] Xenotransplantation elicits salient tumorigenicity of adult T-cell leukemia-derived cells via aberrant AKT activation. (2016)
  • Author(s): Yamaguchi K, Takanashi T, Nasu K, Tamai K, Mochizuki M, Satoh I, Ine S, Sasaki O, Satoh K, Tanaka N, Harigae H, Sugamura K.
  • Journal Title: Cancer Sci. Volume: ePub Issue: 5 Pages: 638-643
  • DOI: 10.1111/cas.12921
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of TL-Om1, an ATL Cell Line, as a Reference Material for Human T-Lymphotropic Virus 1 Quantitative PCR. (2015)
  • Author(s): Kuramitsu M, Okuma K, Yamagishi M, Yamochi T, Firouzi S, Momose H, Mizukami T, Takizawa K, Araki K, Sugamura K, Yamaguchi K, Watanabe T, Hamaguchi I.
  • Journal Title: Journal of Clinical Microbiology Volume: 53 Issue: 2 Pages: 587-596
  • DOI: 10.1128/jcm.02254-14
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Phosphatidic acid-mediated activation and translocation to the cell surface of sialidase NEU3, promoting signaling for cell migration. (2015)
  • Author(s): Shiozaki K, Takahashi K, Hosono M, Yamaguchi K, Hata K, Shiozaki M, Bassi R, Prinetti A, Sonnino S, Nitta K, Miyagi T.
  • Journal Title: FASEB J Volume: 29 Issue: 5 Pages: 2099-2111
  • DOI: 10.1096/fj.14-262543
  • Peer Reviewed
• [Journal Article] Potentiation of Epidermal Growth Factor-Mediated Oncogenic Transformation by Sialidase NEU3 Leading to Src Activation. (2015)
  • Author(s): Yamamoto K, Takahashi K, Shiozaki K, Yamaguchi K, Moriya S, Hosono M, Shima H, Miyagi T.
  • Journal Title: PLoS One Volume: 10 Issue: 3 Pages: e0120578-e0120578
  • DOI: 10.1371/journal.pone.0120578
  • Peer Reviewed / Open Access
• [Journal Article] OX40 and IL-7 play synergistic roles in the homeostatic proliferation of effector memory CD4+ T cells. (2014)
  • Author(s): Yamaki S, Ine, S, Kawabe T, Okuyama Y, Suzuki N, Soroosh P, Mousavi SF, Nagashima H, Sun S-L, So T, Sasaki T, Harigae H, Sugamura K, Kudo H, Wada M, Nio M, and Ishii N.
  • Journal Title: European Journal of Immunology Volume: 44 Issue: 10 Pages: 3015-3025
  • DOI: 10.1002/eji.201444701
  • Peer Reviewed
• [Journal Article] Circulating miR-483-3p and miR-21 is highly expressed in plasma of pancreatic cancer. (2014)
  • Author(s): Abue, M., Yokoyama, M., Shibuya, R., Tamai, K., Yamaguchi, K., Sato, I., Tanaka, N., Hamada, S., Shimosegawa, T., Sugamura, K., Satoh, K.
  • Journal Title: Int J Oncol Volume: 10 Issue: 2 Pages: 1-9
  • DOI: 10.3892/ijo.2014.2743
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Suppressive expression of CD274 increases tumorigenesis and cancer stem cell phenotypes in cholangiocarcinoma (2014)
  • Author(s): Keiichi Tamai, Mao Nakamura, Masamichi Mizuma, Mai Mochizuki, Misa Yokoyama, Hiroyuki Endo, Kazunori Yamaguchi, Takayuki Nakagawa, Masaaki Shiina, Michiaki Unno, Koji Muramoto, Ikuro Sato, Kennichi Satoh, Kazuo Sugamura, and Nobuyuki Tanaka
  • Journal Title: Cancer Science Volume: 105 Issue: 6 Pages: 667-674
  • DOI: 10.1111/cas.12406
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hepatocyte growth factor regulated tyrosine kinase substrate in the peripheral development and function of B-cells. (2014)
  • Author(s): Nagata T, Murata K, Murata R, Sun SL, Saito Y, Yamaga S, Tanaka N, Tamai K, Moriya K, Kasai N, Sugamura K, Ishii N.
  • Journal Title: Biochem Biophys Res Commun. Volume: 443 Pages: 351-356
  • Peer Reviewed
• [Journal Article] Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. (2013)
  • Author(s): Endo H, Shiroki T, Nakagawa T, Yokoyama M, Tamai K, Yamanami H, Fujiya T, Sato I, Yamaguchi K, Tanaka N, Iijima K, Shimosegawa T, Sugamura K, Satoh K.
  • Journal Title: PlosONE Volume: 8 Issue: 10 Pages: e77070-e77070
  • DOI: 10.1371/journal.pone.0077070
  • Peer Reviewed
• [Journal Article] Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector (2013)
  • Author(s): Horino S, Uchiyama T, So T, Nagashima H, Sun SL, Sato M, Asao A, Haji Y, Sasahara Y, Candotti F, Tsuchiya S, Kure S, Sugamura K, and Ishii N
  • Journal Title: PLoS ONE Volume: 8 Issue: 8 Pages: e71594-e71594
  • DOI: 10.1371/journal.pone.0071594
  • Peer Reviewed
• [Presentation] 白血病悪性化への炭酸脱水酵素CA9の関与 (2016)
  • Author(s): 那須 健太郎、 山口壹範、高梨友香、菅村和夫
  • Organizer: がん支援活動 公開シンポジウム
  • Place of Presentation: 一橋大学一橋講堂（東京都、千代田区）
  • Year and Date: 2016-02-08
• [Presentation] 高造腫瘍能ＡＴＬ細胞における炭酸脱水酵素ＩＸ（ＣＡ９）発現亢進の意義 (2015)
  • Author(s): 那須健太郎、山口壹範、玉井恵一、井根省二、佐々木治、佐藤賢一、田中伸幸、張替秀郎、菅村和夫
  • Organizer: 第７４回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-07
• [Presentation] 免疫不全NOGマウスを用いたヒトがん幹細胞の探索 (2014)
  • Author(s): 菅村和夫
  • Organizer: 第53回日本薬学会東北支部大会
  • Place of Presentation: いわき市
  • Year and Date: 2014-10-05
  • Invited
• [Presentation] 免疫不全NOG マウスにより分画された高造腫瘍性ATL 細胞の性状 解析 (2014)
  • Author(s): 山口壹範、那須健太郎、玉井恵一、佐藤賢一、井根省二、 佐々木治、張替秀郎、田中伸幸、菅村和夫
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] BEX2 は静止期がん幹細胞の維持に重要な役割を果たす (2014)
  • Author(s): 玉井恵一、中村真央、望月麻衣、小鎌直子、横山美沙、山口壹範、佐藤賢一、菅村和夫、田中伸幸
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 下咽頭癌の浸潤におけるCD271 の役割 (2014)
  • Author(s): 望月麻衣、今井隆之、玉井恵一、山口壹範、佐藤賢一、松 浦一登、小鎌直子、横山美沙、菅村和夫、田中伸幸
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] ピルビン酸キナーゼM2(PKM2)は膵癌で高発現し、細胞増殖能を亢進させる (2014)
  • Author(s): 横山美沙、白木健悠、田沼延公、玉井恵一、山口壹範、田中伸幸、菅村和夫、佐藤賢一
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 免疫不全NOGマウスを用いた高造腫瘍性ATL細胞単離法の開発 (2013)
  • Author(s): 山口壹範、玉井恵一、佐藤賢一、井根省二、佐々木治、田中伸幸、菅村和夫
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Remarks] 宮城県立がんセンター研究所 発がん制御研究部
• [Remarks] 宮城県立がんセンター研究所 発がん制御研究部
  • URL: http://www.miyagi-pho.jp/mcc/kenkyu/hatugan-seigyo.html