Identification of regulatory molecules related to the differentiation of glioma stem-like cells by an integrated protoemics.

通过整合蛋白质组学鉴定与神经胶质瘤干细胞样细胞分化相关的调节分子。

• 批准号: 24701007
• 负责人: NAMBU AKIKO
• 金额: $ 2.83万
• 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: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24701007/
• 关键词: がん幹細胞; 分化; 細胞外マトリックス; 接着分子; 脳腫瘍; プロテオミクス; DNAマイクロアレイ; 融合プロテオミクス; 分化ニッチ; プロテオーム; 分化誘導; 細胞接着因子; 腫瘍マーカー

In this study, to clarify the molecular mechanism of GSC differentiation, we established GSC clones having the potential to differentiate into glioblastoma, and subjected to DNA microarray and iTRAQ based integrated proteomics. We combined all of the data obtained from the integrated proteomics by utilizing sequential data mining software. GO analysis revealed that the expression of cell adhesion molecules, including integrin aV, and extracellular matrices (ECMs), such as fibronectin 1, was significantly upregulated during serum-induced GSC differentiation. Combinational treatments with integrin inhibitors and anti-cancer drug temozolomide (TMZ) significantly suppressed early events in GSC differentiation, glioma progression and lead the longer survival of mouse GSC xenograft models. These results indicate that GSCs induce/secrete ECMs to develop microenvironments with serum factors, namely differentiation niches that further stimulate GSC differentiation and proliferation.

在本研究中，为了阐明GSC分化的分子机制，我们建立了具有分化为胶质母细胞瘤潜力的GSC克隆，并进行了DNA微阵列和基于iTRAQ的整合蛋白质组学分析。我们利用顺序数据挖掘软件将从集成蛋白质组学中获得的所有数据结合起来。 GO分析显示，细胞粘附分子（包括整合素aV）和细胞外基质（ECM）（如纤连蛋白1）的表达在血清诱导的GSC分化过程中显着上调。整合素抑制剂和抗癌药物替莫唑胺 (TMZ) 的联合治疗显着抑制了 GSC 分化和神经胶质瘤进展的早期事件，并导致小鼠 GSC 异种移植模型的存活时间更长。这些结果表明，GSC诱导/分泌ECM以形成具有血清因子的微环境，即进一步刺激GSC分化和增殖的分化生态位。

项目成果

Glioma Initiating Cells Form a Differentiation Niche Via the Induction of Extracellular Matrices and Integrin aV

胶质瘤起始细胞通过细胞外基质和整合素 aV 的诱导形成分化生态位

• DOI: 10.1371/journal.pone.0059558
• 发表时间: 2013
• 影响因子: 3.7
• 作者: Akiko Niibori

Epiplakin modifies the motility of the HeLa cells and accumulates at the outer surfaces of 3-D cell clusters.

Epiplakin 改变 HeLa 细胞的运动性并积聚在 3-D 细胞簇的外表面。

• DOI: 10.1111/1346-8138.12076
• 发表时间: 2013
• 影响因子: 3.1
• 作者: Shimada H; Nambu
• 通讯作者: Nambu

Integrated proteomics identified novel activation of dynein IC2-GR-COX-1 signaling in NF1 disease model cells.

整合蛋白质组学鉴定了 NF1 疾病模型细胞中动力蛋白 IC2-GR-COX-1 信号传导的新激活。

• DOI: 10.1074/mcp.m112.024802
• 发表时间: 2013
• 影响因子: 7
• 作者: Hirayama M; Kobayashi D; Mizuguchi S; Morikawa T; Nagayama M; Midorikawa U; Wilson MM; Nambu AN; Yoshizawa AC; Kawano S; Araki N.
• 通讯作者: Araki N.

Integrated Proteomics Identified the Differentiation Niche Induced by Glioma Stem Cells

综合蛋白质组学鉴定了神经胶质瘤干细胞诱导的分化生态位

• 发表时间: 2013
• 作者: A. Niibori Nambu; U Midorikawa; S. Mizuguchi; T. Hide; M. Nagai; Y. Komohara; M. Nagayama; M. Hirayama; D. Kobayashi; H. Nakamura; M. Takeya; J. Kuratsu; N. Araki
• 通讯作者: N. Araki

Epiplakin modifies the motility of the HeLa cells and accumulates at the outer surfaces of 3-D cell clusters

Epiplakin 改变 HeLa 细胞的运动性并积聚在 3-D 细胞簇的外表面

• 发表时间: 2013
• 作者: Shimada H; Nambu
• 通讯作者: Nambu