| Project/Area Number |
18K16595
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 56010:Neurosurgery-related
|
|---|
| Research Institution | Dokkyo Medical University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2024-03-31
|
| Project Status |
Completed (Fiscal Year 2023)
|
| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2021: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
|
|---|
| Keywords | 上皮間葉系移行 / 神経膠腫 / ZEB / MMP9 / ZEB2陰性発現 / ZEB1陽性発現 / TGF / VEGF / FGF / 神経膠肉腫 / microRNA / ZEB1/2 |
|---|
| Outline of Final Research Achievements |
In this study, we identified that epithelial-mesenchymal transition mechanism is associated with the transition to a sarcoma-like phenotypic, dissemination, and metastasis of glioblastoma cells. In addition to the transcription factors Slug and TWIST, which have previously been implicated, the high expression of ZEB2 was found in glioblastoma cells. MMP9 was considered to act as a downstream factor of Slug, TWIST and ZEB2. The cadherin switching is considered to the important mechanism causing the reduce of intercellular adhesion in tumor invasion, but not in the phenotypic transformation of glioblastomas.
|
| Academic Significance and Societal Importance of the Research Achievements |
腫瘍細胞が他臓器へ転移、浸潤するには、浸潤先の環境に適応する必要がある。細胞自体の形質を転換する上皮間葉系移行は、この環境適応のために重要なメカニズムの一つと考えられている。本研究の結果は、脳悪性腫瘍の代表である神経膠腫において、この間葉系メカニズムが腫瘍浸潤に関与していることを示唆した。上皮間葉系移行関連転写因子である、Slug, TWIST, ZEB2、その下流因子であるMMP9が重要因子として同定された。腫瘍浸潤に関連する分子同定は、将来の分子標的治療へと繋がる研究結果である。
|
