Elucidation of the molecular basis and therapeutic targets for cancer stem cells through establishing their synthetic niche mimicries

2014 Fiscal Year Final Research Report

• Project Area: Development of Novel Treatment Strategies Targeting Cancer Stem Cells
• Project/Area Number: 22130008
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• 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)
• Co-Investigator(Renkei-kenkyūsha): KAGAWA Tetsushi 東京医科歯科大学, 難治疾患研究所, 准教授 (50270484) ; NOBUHISA Ikuo 東京医科歯科大学, 難治疾患研究所, 准教授 (40332879) ; TABU Kouichi 東京医科歯科大学, 難治疾患研究所, 特任助教 (10466469)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: 癌 / 癌幹細胞 / グリオーマ / ニッチ / ポリマー / マクロファージ / TAM / 鉄

Outline of Final Research Achievements

CSCs have been postulated as key drivers of cancer relapse and progression, and are supposed to be maintained under the specialized microenvironment called niche. To explore the niche mimicry for rat C6 glioma side population (SP) cells (recognized as CSCs), nearly 400 types of acrylate- and urethane-based synthetic polymers were examined. We found that urethane-based PU10 polymer exhibited the highest niche activity in supporting C6 CSCs. TOF/MS analysis of PU10-bound proteins identified an iron carrier transferrin (Tf). Iron is stored in tumor infiltrating CD204+ macrophages, whose protumoral activity is potently enhanced by CSC-secreted soluble factors. Supportively, the clinical data of 376 glioma patients obtained from NCI (USA) database revealed that expressions of Tf receptor and CD204 genes are found to be predictive of glioma patients' malignancies. Our findings will help elucidate the complex nature of the CSC niche and provide novel therapeutic targets to eradicate cancers.

Free Research Field

幹細胞生物学