Development of the the innovative treatment and the proposal of the Self-niche hypothesis in refractory cancer

• Project/Area Number: 16K15620
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: MAEHARA Yoshihiko 九州大学, 医学研究院, 教授 (80165662)
• Co-Investigator(Kenkyū-buntansha): 米満 吉和 九州大学, 薬学研究院, 教授 (40315065) ; 沖 英次 九州大学, 大学病院, 助教 (70380392) ; 佐伯 浩司 九州大学, 大学病院, 助教 (80325448) ; 原田 結 九州大学, 薬学研究院, 助教 (00608507)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: cancer stem cell / niche / irinotecan / がん幹細胞 / ニッチ / 抗がん剤耐性 / 薬剤耐性 / 消化器がん

Outline of Final Research Achievements

To find and investigate stem cell niche for the maintenance of stem cells, colon cancer cell line PLR123 was treated with irinotecan and the remnant cells were sorted into SP and non-SP fractions, and analyze expression levels of mRNA and protein. In cell sorter, SP fraction increased after treatment with irinotecan. ABC transporter and cytokeratin RNAs were upregulated in cancer cells of SP fraction in the microarray. We confirmed the CK20 and BCRP (Breast Cancer Resistance Protein) expression with immunohistochemistry in the cell block of PLR123 irinotecan treated cell. We will elucided the existence of niche-like cells and identify the key molecule which needed to form the niche.

Research Products

• [Journal Article] DOCK1 inhibition suppresses cancer cell invasion and macropinocytosis induced by self-activation Rac1P29S mutation. (2018)
  • Author(s): Tomino T, Tajiri H, Tatsuguchi T, Shirai T, Oisaki K, Matsunaga S, Sanematsu F, Sakata D, Yoshizumi T, Maehara Y, Kanai M, Cote JF, Fukui Y, Uruno T
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 497 Issue: 1 Pages: 298-304
  • DOI: 10.1016/j.bbrc.2018.02.073
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Protein Expression of Programmed Death 1 Ligand 1 and HER2 in Gastric Carcinoma (2017)
  • Author(s): Oki Eiji、Okano Shinji、Saeki Hiroshi、Umemoto Yuichiro、Teraishi Koji、Nakaji Yu、Ando Koji、Zaitsu Yoko、Yamashita Nami、Sugiyama Masahiko、Nakashima Yuichiro、Ohgaki Kippei、Oda Yoshinao、Maehara Yoshihiko
  • Journal Title: Oncology Volume: 93 Issue: 6 Pages: 387-394
  • DOI: 10.1159/000479231
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Characterization of drug resistant cancer stem-like cells and elucidation of the maintenance mechanisms (2017)
  • Author(s): 小野尚美、原田結、佐伯浩司、沖英次、米満吉和、前原喜彦
  • Organizer: 日本消化器がん発生学会
• [Presentation] 薬剤耐性がん幹細胞様細胞の動態変化とその維持機構 (2016)
  • Author(s): 小野尚美、原田結、佐伯浩司、沖英次、米満吉和、前原喜彦
  • Organizer: 第27回日本消化器癌発生学会総会
  • Place of Presentation: 鹿児島県鹿児島市城山観光ホテル
  • Year and Date: 2016-09-15