Identification and functional analysis of glycoprotein factors involved in niche regulation of glioma initiating cell

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K07199
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Kumamoto University
• Principal Investigator: NAMBU AKIKO 熊本大学, 大学院生命科学研究部(医), 特別研究員 (40572087)
• Co-Investigator(Kenkyū-buntansha): 荒木 令江 熊本大学, 大学院生命科学研究部(医), 准教授 (80253722)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: がん幹細胞 / グリオーマ / 糖鎖タンパク質 / 分化 / グライコミクス / プロテオミクス

Outline of Final Research Achievements

Glioma stem/initiating cells (GSC/GIC) and their niches are considered responsible for the therapeutic resistance and recurrence of malignant glioma. To clarify the molecular mechanisms of GIC maintenance/differentiation, we performed a unique integrated proteogenomics utilizing GIC clones established from patient tumors having the potential to develop glioblastoma. After the integration and extraction of the transcriptomics/proteomics data, we found that chondroitin sulfate proteoglycan 4 (CSPG4) and its glyco-biosynthetic enzymes were significantly upregulated in GICs. We also show that CSPG4 chondroitin sulfate glyco-chains suppress GIC differentiation. Moreover, CSPG4-integrin interaction induced by chABC which degrades chondroitin sulfate upregulates integrin aV-dependent ERK/MAPK signaling. Our results indicate that CS-CSPG4 regulates the GIC microenvironment for GIC maintenance/differentiation via the CS moiety which controls integrin signaling.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は, GICクローンを用い, ユニークな最先端の融合グライコプロテオミクス解析技術を応用して, GICの維持と分化を司る糖タンパク質を解析する新しい試みである. 本研究の方法論と得られた情報を応用することによって脳腫瘍のみならず, 多種の癌幹細胞に応用して新たな癌治療戦略構築に有用な情報を得ることが可能である. また, GICの維持・分化誘導に関与するニッチ関連分子群および, これらの分子機能が解明され, 脳腫瘍再発のメカニズムの一端が明らかになることにより, 将来的には脳腫瘍の新規治療薬開発や応用研究にに大きく貢献できることが期待される.