| Project/Area Number |
24701007
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Tumor diagnosis
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
NAMBU AKIKO 熊本大学, 大学院生命科学研究部, 研究員 (40572087)
|
|---|
| Research Collaborator |
ARAKI Norie 熊本大学, 大学院生命科学研究部, 准教授 (80253722)
NAGAI Minako 熊本大学, 大学院生命科学研究部, 技術補佐員
|
|---|
| Project Period (FY) |
2012-04-01 – 2014-03-31
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
|---|
| Keywords | 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 |
|---|
| Research Abstract |
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.
|
