| Project/Area Number |
18K07244
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 50010:Tumor biology-related
|
|---|
| Research Institution | Tokyo Medical University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
|---|
| Keywords | がん間質 / がん微小環境 / 多発性骨髄腫 / miRNA / エクソソーム / セクレトーム / セクレトーム解析 / MGUS |
|---|
| Outline of Final Research Achievements |
In this study, we investigated the role of extracellular vesicles (EVs) from BMSCs derived from MM patients (MM-BMSCs). EV-encapsulated miR-10a expression was high while intracellular miR-10a was low in MM-BMSCs. We therefore hypothesized that miR-10a was packaged into EVs that were actively released into the extracellular space. Inhibition of EV release resulted in accumulation of intracellular miR-10a, inhibition of cell proliferation, and induction of apoptosis in MM-BMSCs. In contrast, proliferation and apoptosis of BMSCs derived from healthy individuals were unaffected by inhibition of EV release. Furthermore, miR-10a derived from MM-BMSCs was transferred into MM cells via EVs and enhanced their proliferation. These results suggest that inhibition of EV release induced apoptosis in MM-BMSCs and inhibited MM cell growth, indicating a possible role for MM-BMSC-targeted therapy.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究では機能的、すなわち腫瘍細胞の進展をサポート可能な間質細胞が放出する因子を探索した。そして、がん間質細胞を標的とする治療法の意義として、上皮性のがん細胞ががん間質細胞へと形質転換（Epithelial-mesenchymal transition: EMT）し、高い転移能やアポトーシスに対する抵抗性を獲得してしまうことが知られており、抗がん剤によって腫瘍細胞を抑制できたとしても、がん間質細胞が残存していると再発や治療抵抗性に多大な影響を及ぼすことが予想され、腫瘍細胞とともにがん間質細胞の撲滅が有効的であると考えられる。
|
