| Project/Area Number |
20591716
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Cerebral neurosurgery
|
|---|
| Research Institution | Kagoshima University |
|---|
Principal Investigator |
HIRANO Hirofumi Kagoshima University, 医学部・歯学部附属病院, 講師 (00264416)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KISHIDA Syosei 鹿児島大学, 医歯学総合研究科, 教授 (50274064)
ARITA Kazunori 鹿児島大学, 医歯学総合研究科, 教授 (90212646)
YUNOUE Syunji 鹿児島大学, 医学部・歯学部附属病院, 助教 (20404478)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
KISHIDA Michiko 鹿児島大学, 医歯学総合研究科, 助教 (40274089)
|
|---|
| Research Collaborator |
KAMINO Masayuki 鹿児島大学, 大学院・医歯学総合研究科, 大学院生
|
|---|
| Project Period (FY) |
2008 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | glioma / Wnt-5a / Frizzled / invasion / astrocytic tumor / migration / matrix metalloprotease-2 / RNAi / Wnt / グリオーマ / 低分子標的薬 / Wntシグナル / Wnt5A / Wnt11 |
|---|
| Research Abstract |
Gliomas are one of the most common intracranial tumors. Gliomas exhibit a progression associated with widespread infiltration into surrounding neuronal tissues. However, the molecular mechanisms that stimulate the invasion of glioma cells are not fully understood. We established two cell lines from human glioma cases and analyzed the expression of all Wnt and Frizzled members in these cell lines and other well-known glioma cell lines by real-time PCR study. The mRNA of Wnt-5a and -7b and Frizzled-2, -6 and -7 were overexpressed in glioma cells. The elevation of Wnt-5a expression was most remarkable. Although Wnt-5a is reported to have oncogenic and antioncogenic activity in several cancers, the role of Wnt-5a signaling in human glioma cells remains unclear. Immunohistochemical study also revealed high expression of Wnt-5a in 26 (79%) of 33 human glioma cases. The positivity of Wnt-5a expression was correlated with the clinical grade. Knockdown of Wnt-5a expression suppressed migration, invasion and expression of matrix metalloproteinase-2 of glioma cells. Reciprocally, treatment with purified Wnt-5a ligand resulted in stimulation of cell migration and invasion. MMP-2 inhibitor suppressed the Wnt-5a-dependent invasion of U251 cells. These results suggested that Wnt-5a is not only a prognostic factor but also a therapeutic target molecule in gliomas for preventing tumor cell infiltration.
|
