Establishment of Glioma stem-like cells(GSC) from glioma patient tumors and analysis of the novel molecular markers of GSC by an integrated proteomics.

从神经胶质瘤患者肿瘤中建立神经胶质瘤干样细胞（GSC）并通过综合蛋白质组学分析 GSC 的新型分子标记。

• 批准号: 22700905
• 负责人: NANBU Akiko
• 金额: $ 2.58万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22700905/
• 关键词: プロテオミクス解析; がん幹細胞; 腫瘍マーカー; プロテオーム; 細胞外マトリックス; 分化誘導

Glioma stem cells(GSCs) are thought to be responsible for the therapeutic resistance and recurrence of malignant glioma. The molecules regulating the maintenance/differentiation of these cells are considered effective therapeutic targets. In this study, we established GSC clones from tumors of malignant glioma patients and subjected them to integrated proteomics to survey the proteins and mRNAs differentially expressed in GSCs after they have been induced by serum stimulation. This resulted in the identification of 30000 molecules and GO analysis revealed that the expression of cell adhesion molecules, including integrin subfamily members and extracellular matrices(ECMs) was significantly upregulated during GSC differentiation. After the cell-biological validations, we found that serum factor-induced coupling of ECMs to differentiation and proliferation. The results raised the possibility that GSC induces/secretes ECMs by itself to form a specific microenvironment, called the "differention niche", which facilitates the development of malignant glioma.

胶质瘤干细胞（GSC）被认为是恶性胶质瘤治疗耐药和复发的原因。调节这些细胞的维持/分化的分子被认为是有效的治疗靶标。在这项研究中，我们建立了恶性胶质瘤患者的肿瘤GSC克隆，并对其进行整合蛋白质组学调查GSC差异表达的蛋白质和mRNA后，他们已被血清刺激。这导致在30000分子的鉴定和GO分析表明，细胞粘附分子，包括整合素亚家族成员和细胞外基质（ECM）的表达显着上调GSC分化过程中。经过细胞生物学验证，我们发现血清因子诱导的ECM与分化和增殖偶联。这些结果提示GSC可能通过自身诱导分泌ECM，形成一个特殊的微环境，称为分化小生境，从而促进恶性胶质瘤的发生。

项目成果

融合プロテオミクスによる幹細胞様グリオーマの分化制御機構の解析

融合蛋白质组学分析干细胞样胶质瘤的分化控制机制

• 发表时间: 2011
• 作者: 南部晶子;緑川宇一;水口惣平;長山慈;永井美奈子;平野久;荒木令江
• 通讯作者: 荒木令江

プロテオミクスによるグリオーマ幹細胞分化に関する特異的分子群のプロファイリング解析

使用蛋白质组学对与神经胶质瘤干细胞分化相关的特定分子组进行分析

• 发表时间: 2010
• 作者: 緑川宇一;新堀晶子;水口惣平;新森加納子;丸尾祐二;鵜沼豊;中村眞;荒木令江
• 通讯作者: 荒木令江

Integrated proteomics of cancer cellular activation signals related to chemotherapy resistances

与化疗耐药相关的癌细胞激活信号的综合蛋白质组学

• 发表时间: 2010
• 作者: S. Mizuguchi;T. Morikawa;N. Tsubota;U Midorikawa;A. Niibori;D. Kobayashi;H. Nakamura;J. Kuratsu;N. Araki
• 通讯作者: N. Araki

The functional study of vimentin network involved in chemo sensitivity of gliomas using integrated proteomics data processing/mining approach

使用集成蛋白质组数据处理/挖掘方法研究涉及神经胶质瘤化疗敏感性的波形蛋白网络的功能

• 发表时间: 2010
• 作者: S. Mizuguchi;T. Morikawa;N. Tsubota;U Midorikawa;M. Nagayama;D. Kobayashi;A. Niibori;A. Wilson;M. Wilson Morifuji;H. Nakamura;J. Kuratsu;N. Araki
• 通讯作者: N. Araki