Radiation sensitivity in dormant tumor cells using a novel primary culture system

• Project/Area Number: 25461937
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses
• Principal Investigator: Endo Hiroko 地方独立行政法人大阪府立病院機構大阪府立成人病センター(研究所), 研究所, 研究員 (20359300)
• Co-Investigator(Kenkyū-buntansha): Inoue Masahiro 地方独立行政法人 大阪府立病院機構大阪府立成人病センター(研究所), 研究所, 部長 (10342990)
• 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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 大腸癌 / 放射線感受性 / 休眠状態 / 低酸素 / 分化 / 癌細胞初代培養

Outline of Final Research Achievements

CTOS (cancer tissue-originated spheroid) from colorectal cancer patients entered a reversible dormant status when cultured in hypoxia and growth factor deprived conditions. CTOS retained the characteristics of highly differentiated adenocarcinoma, and the expression of stemness or differentiation genes changed drastically depending on the culture conditions.
In the present study, we established a radiation sensitivity assay using colon cancer CTOS. CTOS in dormant status showed radiation resistance compared to the normal culture conditions, and dormant CTOS showed high expression of stemness and differentiated genes at the same time. In addition to the well-known radio-resistant mechanism, such as cell cycle arrest and hypoxia, dormant CTOS might gain the radiation resistance through the fluctuation of stemness and differentiation.

Research Products

• [Journal Article] Furospinosulin-1, marine spongean furanosesterterpene, suppresses the growth of hypoxia-adapted cancer cells by binding to transcriptional regulators p54nrb and LEDGF/p75. (2016)
  • Author(s): Arai, M.; Kawachi, T.; Kotoku, N.; Nakata, C.; Kamada, H.; Tsunoda, S.; Tsutsumi, Y.; Endo, H.; Inoue, M.; Sato, H.; Kobayashi, M.
  • Journal Title: ChemBioChem Volume: 17 Issue: 2 Pages: 181-189
  • DOI: 10.1002/cbic.201500519
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immuno-PET Imaging of HER3 in a Model in which HER3 Signaling Plays a Critical Role (2015)
  • Author(s): Yuan Q, Furukawa T, Tashiro T, Okita K, Jin ZH, Aung W, Sugyo A, Nagatsu K, Endo H, Tsuji AB, Zhang MR, Masuko T, Inoue M, Fujibayashi Y, Saga T.
  • Journal Title: PloS one Volume: 10 Issue: 11 Pages: e0143076-e0143076
  • DOI: 10.1371/journal.pone.0143076
  • Peer Reviewed / Open Access
• [Journal Article] Dynamic Change in p63 Protein Expression during Implantation of Urothelial Cancer Clusters. (2015)
  • Author(s): Yoshida T, Okuyama H, Nakayama M, Endo H, Tomita Y, Nonomura N, Nishimura K, Inoue M.
  • Journal Title: Neoplasia Volume: 17 Issue: 7 Pages: 574-585
  • DOI: 10.1016/j.neo.2015.07.004
  • Peer Reviewed / Open Access
• [Journal Article] A limited overlap between intratumoral distribution of 1-(5-fluoro-5-deoxy-alpha-D-arabinofuranosyl)-2-nitroimidazole and copper-diacetyl-bis[N(4)-methylthiosemicarbazone] (2015)
  • Author(s): Furukawa T, Yuan Q, Jin ZH, Aung W, Yoshii Y, Hasegawa S, Endo H, Inoue M, Zhang MR, Fujibayashi Y, Saga T.
  • Journal Title: Oncol Rep. Volume: 34 Issue: 3 Pages: 1379-1387
  • DOI: 10.3892/or.2015.4079
  • Peer Reviewed
• [Journal Article] Analysis of ERBB ligand-induced resistance mechanism to crizotinib by primary culture of lung adenocarcinoma with EML4-ALK fusion gene. (2015)
  • Author(s): Kimura M, Endo H, Inoue T, Nishino K, Uchida J, Kumagai T, Kukita Y, Kato K, Imamura F, Inoue M
  • Journal Title: Journal of Thoracic Oncology Volume: 10 Issue: 3 Pages: 527-30
  • DOI: 10.1097/jto.0000000000000381
  • Peer Reviewed / Open Access
• [Journal Article] Dormancy of cancer cells with suppression of AKT activity contributes to survival in chronic hypoxia (2014)
  • Author(s): Endo H, Okuyama H, Ohue M, Inoue M
  • Journal Title: PLoS ONE Volume: 9 Issue: 6 Pages: e98858-e98858
  • DOI: 10.1371/journal.pone.0098858
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Radiation sensitivity assay with a panel of patient-derived spheroids of small cell carcinoma of the cervix. (2014)
  • Author(s): Nakajima A, Endo H, Okuyama H, Kiyohara Y, Kimura T, Kamiura S, Hiraoka M, Inoue M.
  • Journal Title: Int J Cancer Volume: - Issue: 12 Pages: 2949-2960
  • DOI: 10.1002/ijc.29349
  • Peer Reviewed
• [Presentation] MIG6 contributes to hypoxia-induced dormancy in primary cultured lung cancer cells with EGFR active mutation (2015)
  • Author(s): 遠藤 洋子
  • 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: 2015-10-08
• [Presentation] MIG6はEGFR活性変異型肺がん細胞の低酸素による休眠状態誘導に寄与する (2015)
  • Author(s): 遠藤 洋子
  • Organizer: 第13回がんとハイポキシア研究会
  • Place of Presentation: 国立遺伝学研究所
  • Year and Date: 2015-06-05
• [Presentation] 肺がん初代培養細胞における低酸素下休眠状態の誘導メカニズム (2014)
  • Author(s): 遠藤 洋子
  • Organizer: 第12回 がんとハイポキシア研究会
  • Place of Presentation: ホテルマリターレ創世佐賀
  • Year and Date: 2014-11-20 – 2014-11-21
• [Presentation] 低酸素環境下における癌細胞の休眠状態の誘導 (2014)
  • Author(s): 遠藤 洋子
  • Organizer: 第二回 癌と代謝研究会
  • Place of Presentation: 東京理科大学 葛飾キャンパス
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] Inactive status of cancer cells with suppression of AKT activity contributes to survival in chronic hypoxia (2014)
  • Author(s): 井上 正宏
  • Organizer: AACR Annual Meeting
  • Place of Presentation: San Diego Convention Center
• [Presentation] 癌細胞初代培養系（CTOS）における低酸素による休眠状態の誘導 (2013)
  • Author(s): 遠藤 洋子
  • Organizer: 第11回がんとハイポキシア研究会
  • Place of Presentation: 東北大学 片平さくらホール
• [Remarks] 大阪府立成人病センター研究所 生化学部門
  • URL: http://www.mc.pref.osaka.jp/omc2/category/biochemistry.html
• [Remarks] 大阪府立成人病センター研究所 部門紹介 生化学部門
  • URL: http://www.mc.pref.osaka.jp/omc2/category/biochemistry.html