Creation of 3D cancer tissue model using high-strength porous gel and development of new cancer stem cell-targeted therapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03802
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Hokkaido University
• Principal Investigator: Tsuda Masumi 北海道大学, 医学研究院, 准教授 (30431307)
• Co-Investigator(Kenkyū-buntansha): 野々山 貴行 北海道大学, 先端生命科学研究院, 准教授 (50709251) ; 田中 伸哉 北海道大学, 医学研究院, 教授 (70261287)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: がん幹細胞

Outline of Final Research Achievements

Cancer stem cells are thought to be created and survive in a special microenvironment (cancer stem cell niche) in cancer tissues and cause cancer recurrence; however, the details are unknown. In this research, based on the hydrogel-based cancer stem cell reprogramming technique that we have recently developed, we created cancer stem cell niches utilizing the hydrogel in order to mimic cancer stem cell reprogramming in cancer tissues, and analyzed the creation and survival mechanisms of cancer stem cells. Glioblastoma cells promoted reprogramming through direct interaction with vascular endothelial cells. In addition, they adhered to astrocytes and proliferated dominantly, and secreted proteins derived from astrocytes increased stemness of glioblastoma cells. Furthermore, through drug screening, we identified several drugs that is effective against glioblastoma stem cells.

Free Research Field

実験病理学、がん生物学

Academic Significance and Societal Importance of the Research Achievements

ヒト膠芽腫細胞では低栄養環境および血管内皮細胞との直接接触がリプログラミングを促進した。膠芽腫では特徴的な微小血管増生や糸球体様血管束が認められ、その周囲ではpalisading necrosis(低酸素、低栄養環境)が認められることから、癌幹細胞が生成・生存しやすい環境が整っていることが示唆された。また、アストロサイト由来の分泌蛋白が幹細胞性を増加させたことから、脳に存在する支持細胞が至適な環境下で腫瘍の幹細胞性を誘導し、がん幹細胞の生存に有利に機能していることが示唆された。膠芽腫幹細胞に対して効果が認められた薬剤は、高悪性度の膠芽腫に対して生命予後を改善できる可能性があると期待される。