Elucidation of the molecular basis for the cancer stem cell niche

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04292
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TAGA Tetsuya 東京医科歯科大学, 難治疾患研究所, 教授 (40192629)
• Research Collaborator: BRADLEY Mark University of Edinburgh, School of Chemistry, Professor
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 癌 / 癌幹細胞 / ニッチ / グリオーマ / 膵臓癌 / ヘム / 鉄 / 5-ALA

Outline of Final Research Achievements

Cancer stem cells (CSCs) reside in a microenvironment, niche. Elucidation of the CSC niche helps develop new cancer therapy. We have identified a CSC niche-mimicking polymer from 376 synthetic polymers and identified an iron-carrier transferrin (Tf) which binds to it. In the tumor formed in the mouse brain following transplantation of rat C6 glioma CSCs, iron was found to be stored in tumor-associated macrophages (TAMs), suggesting contribution of iron-storing TAMs to cancer progression. We further demonstrated that CSCs recruit monocytes and induce their differentiation into TAMs. Since PpIX, a fluorescent metabolite of 5-ALA, accumulates in glioma cells, 5-ALA is used for fluorescence-guided surgical resection. We indicated that CSCs exhibit low PpIX accumulation among glioma cells via nonfluorescent conversion by iron incorporated by Tf receptor, suggesting that CSCs escape from surgical resection. We propose that glioma CSCs have a capacity to construct self-advantageous niche.

Free Research Field

幹細胞生物学