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，我们建立了具有向胶质母细胞瘤分化潜力的GSC克隆，并进行了DNA微阵列和基于iTRAQ的整合蛋白质组学研究。我们利用序列数据挖掘软件将整合蛋白质组学获得的所有数据进行组合。氧化石墨烯分析显示，在血清诱导的GSC分化过程中，细胞粘附分子（包括整合素aV）和细胞外基质（ecm）（如纤维连接蛋白1）的表达显著上调。整合素抑制剂和抗癌药物替莫唑胺（TMZ）联合治疗可显著抑制GSC分化和胶质瘤进展的早期事件，并延长小鼠GSC异种移植模型的存活时间。这些结果表明，GSCs诱导/分泌ecm形成具有血清因子的微环境，即分化壁龛，进一步刺激GSC分化和增殖。

项目成果

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

• DOI: 10.1111/1346-8138.12076
• 发表时间: 2013-04-01
• 期刊: JOURNAL OF DERMATOLOGY
• 影响因子: 3.1
• 作者: Shimada, Hiromitsu;Nambu-Niibori, Akiko;Fujiwara, Sakuhei
• 通讯作者: Fujiwara, Sakuhei

Glioma initiating cells form a differentiation niche via the induction of extracellular matrices and integrin αV.

• DOI: 10.1371/journal.pone.0059558
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Niibori-Nambu A;Midorikawa U;Mizuguchi S;Hide T;Nagai M;Komohara Y;Nagayama M;Hirayama M;Kobayashi D;Tsubota N;Takezaki T;Makino K;Nakamura H;Takeya M;Kuratsu J;Araki N
• 通讯作者: Araki N

神経線維腫症2型

2 型神经纤维瘤病

• 发表时间: 2013
• 作者: 荒木令江;南部晶子;小林大樹
• 通讯作者: 小林大樹

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 信号的新激活

• 发表时间: 2013
• 期刊: Mol Cell Proteomics
• 影响因子: 7
• 作者: Hirayama M;Kobayashi D;Mizuguchi S;Morikawa T;Nagayama M;Midorikawa U;Wilson MM;Nambu Akiko Niibori;Yoshizawa AC;Kawano S;Araki N
• 通讯作者: Araki N

Contribution of RIZ1 to regulation of proliferation and migration of a liver fluke-related cholangiocartinoma cell

RIZ1 对肝吸虫相关胆管细胞瘤细胞增殖和迁移的调节作用

• 发表时间: 2012
• 期刊: Asian Pac J Cancer Prev
• 作者: Khaenam P;Niibori A ;Okada S;Jearanaikoon P;Araki N;Limpaiboon T
• 通讯作者: Limpaiboon T