Targeting Rab family small G proteins as a novel neuroblastoma therapeutic approach

• Project/Area Number: 26461584
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kobe University
• Principal Investigator: Nishimura Noriyuki 神戸大学, 医学研究科, 特命教授 (00322719)
• Co-Investigator(Kenkyū-buntansha): 早川 晶 神戸大学, 医学研究科, 医学研究員 (40379376) ; 西尾 久英 神戸大学, 医学研究科, 教授 (80189258)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 神経芽腫 / がん幹細胞 / 微小残存病変(MRD) / Rab / 間葉系幹細胞(MSC) / ALDH

Outline of Final Research Achievements

More than half of high-risk neuroblastoma patients have experienced tumor relapses and their overall survival rates remain less than 40%. To improve their prognosis, it is necessary to develop a novel therapeutic approach targeting minimal residual disease (MRD) comprised of chemoresistant cancer stem cells (CSCs). In the present study, we have identified a member of Rab family small G proteins (Rabs), which control the development of neuroblastoma CSCs, and its effector protein. We have then characterized their upstream/downstream signaling pathways.

Research Products

• [Journal Article] Collaboration of cancer-associated fibroblasts and tumour-associated macrophages for neuroblastoma development (2016)
  • Author(s): Hashimoto O, Yoshida M, Koma Y, Yanai T, Hasegawa D, Kosaka Y, Nishimura N, Yokozaki H
  • Journal Title: J Pathol Volume: 240 Issue: 2 Pages: 211-223
  • DOI: 10.1002/path.4769
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Early detection of tumor relapse/re-growth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients. (2016)
  • Author(s): Hirase S, Saitoh A, Hartomo TB, Kozaki A, Yanai T, Hasegawa D, Kawasaki K, Kosaka Y, Matsuo M, Yamamoto N, Mori T, Hayakawa A, Iijima K, Nishio H, and Nishimura N.
  • Journal Title: Oncol Let Volume: 12 Issue: 2 Pages: 1119-1123
  • DOI: 10.3892/ol.2016.4682
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Involvement of aldehyde dehydrogenase 1A2 in the regulation of cancer stem cell properties in neuroblastoma. (2015)
  • Author(s): Hartomo TB, Pham TVH, Yamamoto N, Hirase S, Hasegawa D, Kosaka Y, Matsuo M, Hayakawa A, Takeshima Y, Iijima K, Nishio H, and Nishimura N.
  • Journal Title: Int J Oncol Volume: 46 Issue: 3 Pages: 1089-1098
  • DOI: 10.3892/ijo.2014.2801
  • Peer Reviewed
• [Journal Article] Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients. (2015)
  • Author(s): Yamamoto N, Kozaki A, Hartomo TB, Yanai T, Hasegawa D, Kawasaki K, Kosaka Y, Matsuo M, Hirase S, Mori T, Hayakawa A, Iijima K, Nishio H, and Nishimura N.
  • Journal Title: Oncol Let Volume: 10 Issue: 5 Pages: 3228-3232
  • DOI: 10.3892/ol.2015.3710
  • Peer Reviewed
• [Presentation] DENN domain protein DENND2A regulates the progression of neuroblastoma. (2016)
  • Author(s): Yamamoto N, Thwin KK, Fujimura J, Nakanishi K, Mori T, Hayakawa A, Nishio H, Matsuo M, Hasegawa D, Kawasaki K, Kosaka Y, Iijima K, and Nishimura N.
  • Organizer: Advances in Neuroblastoma Research Conference 2016
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2016-06-19
  • Int'l Joint Research
• [Presentation] Rab6B mediates the progression of neuroblastoma through the interaction with MTMR5. (2016)
  • Author(s): Nishimura N, Pham TVH, Thwin KK, Yamamoto N, Mori T, Hayakawa A, Nishio H, Matsuo M, Hasegawa D, Kawasaki K, Kosaka Y, and Iijima K.
  • Organizer: Advances in Neuroblastoma Research Conference 2016
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2016-06-19
  • Int'l Joint Research
• [Presentation] 神経芽腫患者の微小残存病変モニタリング (2016)
  • Author(s): 西村範行, Khin Kyaemon Thwin, 山本暢之, 森健, 早川晶, 長谷川大一郎, 川崎圭一郎, 小阪嘉之, 西尾久英, 飯島一誠.
  • Organizer: 第119回日本小児科学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2016-05-13
• [Presentation] Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients. (2015)
  • Author(s): Uemura S, Yamamoto N, Kozaki A, Nino N, Takafuji S, Yokoi T, Saito A, Ishida T, Hasegawa D, Kawasaki K, Kosaka Y, Mori T, Hayakawa A, Iijima K, Nishio H, and Nishimura N.
  • Organizer: 第57回日本小児血液・がん学会学術集会
  • Place of Presentation: 山梨
  • Year and Date: 2015-11-27
• [Presentation] 神経芽腫の発症・進展におけるRab6BとRab28の役割. (2015)
  • Author(s): 西村範行, 山本暢之, 長谷川大一郎.
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] DENNドメイン蛋白質DENND2Aによる神経芽腫の発症・進展の制御機構. (2015)
  • Author(s): 山本暢之, 西村範行, 長谷川大一郎.
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] Two high-risk neuroblastoma cases with early detection of tumor relapse/re-growth by consecutive minimal residual disease monitoring. (2015)
  • Author(s): Saito A, Hirase S, Kozaki A, Yanai T, Hasegawa D, Kawasaki K, Kosaka Y, Hayakawa A, Iijima K, Nishio H, and Nishimura N.
  • Organizer: 11th Asian Society for Pediatric Research
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-15
  • Int'l Joint Research
• [Presentation] Neuroblastoma minimal residual disease markers are differentially expressed in peripheral blood and bone marrow samples. (2015)
  • Author(s): Uemura S, Yamamoto N, Kozaki A, Yanai T, Hasegawa D, Kawasaki K, Kosaka Y, Hayakawa A, Iijima K, Nishio H, and Nishimura N.
  • Organizer: 11th Asian Society for Pediatric Research
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-15
  • Int'l Joint Research
• [Presentation] 神経芽腫がん幹細胞の発生・分化における細胞内小胞輸送の制御因子Rab6Bの役割. (2014)
  • Author(s): 西村範行, Thi Van Huyen Pham, Tri Budi Hartomo, 山本暢之, 平瀬敏志, 早川晶, 矢内友子, 長谷川大一郎, 川崎圭一郎, 小阪嘉之, 松尾雅文, 飯島一誠, 西尾久英.
  • Organizer: 第56回日本小児血液・がん学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2014-11-28 – 2014-11-30
• [Presentation] Aldehyde dehydrogenase ALDH1A2 regulates cancer stem cell properties in neuroblastoma. (2014)
  • Author(s): Nishimura N, Hartomo TB, Pham TVH, Yamamoto N, Hirase S, Hayakawa A, Yanai T, Hasegawa D, Kawasaki K, Kosaka Y, Matsuo M, Iijima K, Nishio H.
  • Organizer: 第56回日本小児血液・がん学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2014-11-28 – 2014-11-30
• [Presentation] Aldehyde dehydrogenase 1A2 expression correlates with cancer stem cell properties in neuroblastoma. (2014)
  • Author(s): Nishimura N, Hartomo TB, Pham TVH, Yamamoto N, Hirase S, Hayakawa A, Hasegawa D, Kawasaki K, Kosaka Y, Matsuo M, Takeshima Y, Iijima K, and Nishio H.
  • Organizer: Advances in Neuroblastoma Research Conference 2014
  • Place of Presentation: Cologne, Germany
  • Year and Date: 2014-05-13 – 2014-05-16
• [Presentation] Induction of ALDH1A2 expression is critical for cancer stem cell properties in neuroblastoma. (2014)
  • Author(s): Nishimura N, Hartomo TB, Pham TVH, Yamamoto N, Hirase S, Hayakawa A, Hasegawa D, Kawasaki K, Kosaka Y, Matsuo M, Takeshima Y, Iijima K, and Nishio H.
  • Organizer: AACR Annual Meeting 2014
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2014-04-05 – 2014-04-09