Analysis of epigenetic regulation by visualizing S-adenosylmethionine metabolism in cancer cells using imaging mass spectrometry.

• Project/Area Number: 25513008
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: オミクス計測科学
• Research Institution: Keio University
• Principal Investigator: Kubo Akiko 慶應義塾大学, 医学部, 講師 (50455573)
• Co-Investigator(Renkei-kenkyūsha): YAMAMOTO Takehiro 慶應義塾大学, 医学部, 講師 (50383774)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: メタボロミクス / 質量分析イメージング / エピジェネティクス

Outline of Final Research Achievements

In this study, we focused on S-adenosylmethionine (SAM) metabolism. SAM is the only substrate in which is used in all the methylation reaction in vivo. In an experimental model of xenograft transplantation of human colon cancer HCT116 cells in superimmunodeficient NOG mice, snap-frozen liver tissues containing metastatic tumors were examined by quantitative-imaging mass spectrometry. As reported previously, short hairpin CD44 RNA interference (shCD44) in cancer cells caused significant regression of tumor growth in the host liver. Under these circumstances, the CD44 knockdown suppressed polyamines (polyamines are biosynthesized from SAM), GSH and energy charges.

Research Products

• [Journal Article] Therapeutic hypothermia achieves neuroprotection via a decrease in acetylcholine with a concurrent increase in carnitine in the neonatal hypoxia-ischemia (2015)
  • Author(s): 2.Takenouchi T, Sugiura Y, Morikawa T, Nakanishi T, Nagahata Y, Sugioka T, Honda K, Kubo A, Hishiki T, Matsuura T, Hoshino T, Takahashi T, Suematsu M, and Kajimura M
  • Journal Title: Journal of Cerebral Blood Flow & Metabolism Volume: 35 Issue: 5 Pages: 1-12
  • DOI: 10.1038/jcbfm.2014.253
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of the Oxygen Sensor PHD2 in the Liver Improves Survival in Lactic Acidosis by Activating the Cori Cycle (2015)
  • Author(s): Suhara T, Hishiki T, Kasahara M, Hayakawa N, Oyaizu T, Nakanishi T, Kubo A, Morisaki H, Kaelin WG Jr., Suematsu M, Minamishima YA§. (§Corresponding author)
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 112 Issue: 37 Pages: 11642-7
  • DOI: 10.1073/pnas.1515872112
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Large-area surface-enhanced Raman spectroscopy imaging of brain ischemia by gold nanoparticles grown on random nanoarrays oftransparent boehmite, (2015)
  • Author(s): 1.Yamazoe S, Naya M, Shiota M, Morikawa M, Kubo A, Tani T, Hishiki T, Horiuchi T, Suematsu M, and Kajimura M
  • Journal Title: ACS Nano Volume: 8 Issue: 6 Pages: 5622-5632
  • DOI: 10.1021/nn4065692
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Impacts of CD44 knockdown in cancer cells on tumor and host metabolic systems revealed by quantitative imaging mass spectrometry. (2014)
  • Author(s): Ohmura M, Hishiki T, Yamamoto T, Nakanishi T, Kubo A, Tsuchihashi K, Tamada M, Toue S, Kabe Y, Saya H and Suematsu M
  • Journal Title: Nitric Oxide Volume: pii: S1089-8603 Pages: 495-499
  • DOI: 10.1016/j.niox.2014.11.005
  • Peer Reviewed / Open Access
• [Journal Article] 「持ちつ持たれつ・・・がんの代謝」―グルタミノリシス (2014)
  • Author(s): 久保亜紀子
  • Journal Title: 実験医学増刊 Volume: 32 Pages: 92-98
• [Journal Article] Microscopic imaging mass spectrometry assisted by on-tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts. (2014)
  • Author(s): Toue S, Sugiura Y, Kubo A, Ohmura M, Karakawa S, Mizukoshi T, Yoneda J, Miyano H, Noguchi Y, Kobayshi T, Kabe Y, Suematsu M.
  • Journal Title: Proteomics Volume: 14 Issue: 7-8 Pages: 810-819
  • DOI: 10.1002/pmic.201300041
  • Peer Reviewed
• [Journal Article] Reduced methylation of PFKFB3 in cancer cells shunts glucose towards the pentose phosphate pathway. (2014)
  • Author(s): Takehiro Yamamoto, Naoharu Takano, Kyoko Ishiwata, Mitsuyo Ohmura, Yoshiko Nagahata, Tomomi Matsuura, Aki Kamata, Kyoko Sakamoto, Tsuyoshi Nakanishi, Akiko Kubo, Takako Hishiki, and Makoto Suematsu.
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 3480-3480
  • DOI: 10.1038/ncomms4480
  • Peer Reviewed
• [Journal Article] Energy management by enhanced glycolysis in G1-phase in human colon cancer cells in vitro and in vivo. (2013)
  • Author(s): Bao Y, Mukai K, Hishiki T, Kubo A, Ohmura M, Sugiura Y, Matsuura T, Nagahata Y, Hayakawa N, Yamamoto T, Fukuda R, Saya H, Suematsu M, Minamishima YA.
  • Journal Title: Mol Cancer Res. Volume: 11 Issue: 9 Pages: 973-985
  • DOI: 10.1158/1541-7786.mcr-12-0669-t
  • Peer Reviewed
• [Presentation] ヒト大腸がん肝転移病巣のin vivo細胞周期依存的エネルギー代謝を質量分析イメージングで可視化する (2015)
  • Author(s): 久保亜紀子・鮑彦・向井邦晃・菱木貴子・大村光代・南嶋洋司・末松誠
  • Organizer: 第８８回日本生化学会大会(BMB2015)
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 担がん組織切片における過硫化グルタチオン蓄積の質量イメージングによる評価 (2015)
  • Author(s): 久保亜紀子・大村光代・中西 豪・菱木貴子・山本雄広・末松 誠
  • Organizer: 第63回質量分析総合討論会
  • Place of Presentation: つくば国際会議場 エポカルつくば（茨城県つくば市）
  • Year and Date: 2015-06-17
• [Presentation] Detection of ammonia on human colon cancer-bearing livers of superimmunideficient NOG mice by MALDI MS imaging (2014)
  • Author(s): 久保亜紀子・大村 光代・中西 豪・末松 誠
  • Organizer: 第62回American Society of Mass Spectrometry 年会
  • Place of Presentation: ボルチモア（米国）
  • Year and Date: 2014-06-17
• [Presentation] 生体組織切片に含まれるアンモニアの質量イメージング法による評価 (2014)
  • Author(s): 久保亜紀子・大村 光代・中西 豪・末松 誠
  • Organizer: 第62回質量分析総合討論会
  • Place of Presentation: ホテル阪急エキスポパーク（大阪府吹田市）
  • Year and Date: 2014-05-16
• [Presentation] ヒト大腸がん細胞のin vitro同調培養およびin vivoにおける細胞周期依存的エネルギー代謝 (2013)
  • Author(s): 久保亜紀子・鮑彦・向井邦晃・菱木貴子・大村光代・南嶋洋司・末松誠
  • Organizer: 第61回質量分析総合討論会
  • Place of Presentation: つくば国際会議場 エポカルつくば
• [Patent(Industrial Property Rights)] 分析データ表示処理装置及び表示処理プログラム (2015)
  • Inventor(s): 後藤信一 梶村眞弓 久保亜紀子 末松誠 池上将弘 緒方是嗣
  • Industrial Property Rights Holder: 後藤信一 梶村眞弓 久保亜紀子 末松誠 池上将弘 緒方是嗣
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-161543
  • Filing Date: 2015-08-19
• [Patent(Industrial Property Rights)] MALDI 用試料調製方法及び試料調製装置 (2015)
  • Inventor(s): 緒方是嗣 高橋和輝 久保亜紀子 末松誠 山本卓志
  • Industrial Property Rights Holder: 緒方是嗣 高橋和輝 久保亜紀子 末松誠 山本卓志
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-510153
  • Filing Date: 2015-10-02
  • Overseas
• [Patent(Industrial Property Rights)] MALDI 用試料調製方法及び試料調製装置 (2014)
  • Inventor(s): 緒方是嗣 高橋和輝 久保亜紀子 末松誠 山本卓志
  • Industrial Property Rights Holder: 緒方是嗣 高橋和輝 久保亜紀子 末松誠 山本卓志
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-04-04
• [Patent(Industrial Property Rights)] 質量分析を用いたアンモニア測定方法 (2013)
  • Inventor(s): 久保亜紀子 末松誠 緒方是嗣
  • Industrial Property Rights Holder: 久保亜紀子 末松誠 緒方是嗣
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-209000
  • Filing Date: 2013-10-04