| Project/Area Number |
17K10972
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Kagoshima University |
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Principal Investigator |
Sasaki Hiromi 鹿児島大学, 医歯学域鹿児島大学病院, 助教 (60773380)
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| Co-Investigator(Kenkyū-buntansha) |
前田 真吾 鹿児島大学, 医歯学総合研究科, 特任准教授 (60353463)
永野 聡 鹿児島大学, 医歯学域医学系, 准教授 (50373139)
小宮 節郎 鹿児島大学, 医歯学域医学系, 教授 (30178371)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 軟骨肉腫 / TGF-β / SLC14A1 / PEG10 / UT-B / 尿素 / 尿素輸送体 |
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| Outline of Final Research Achievements |
Histological distinction between enchondroma and chondrosarcoma is difficult because of a lack of definitive biomarkers.
We examined TGF-βsignaling and downstream genes including Solute Carrier Family 14 Member 1(SLC14A1) and Paternally expressed gene 10 (PEG10) identified by microarray analysis are useful biomarkers in differentiation with chondrosarcoma and enchondroma. Highly active TGF-βsignaling and BMP signaling and concurrent downregulation of SCL14A1 and PEG10 in human chondrosarcoma samples were found in human chondrosarcoma samples. PEG10 expression was suppressed by TGF-β signaling, and PEG10 interfered with the TGF-β and BMP-SMAD pathways in chondrosarcoma cells. Our results indicate that expression of PEG10 is an index to distinguish between enchondroma and chondrosarcoma, and the possibility of molecular target for suppressing the aggressive phenotypes of chondrosarcoma cells.
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| Academic Significance and Societal Importance of the Research Achievements |
軟骨肉腫は、化学療法や放射線治療に抵抗性であり有用な治療は手術療法のみである。臨床では肺転移をきたす悪性度の高い軟骨肉腫も存在し、進行期軟骨肉腫に対しては有効な治療がないのが現状である。また、軟骨肉腫、特にgrade1軟骨肉腫は病理学的に良性である内軟骨腫との鑑別が困難であることが問題である。今回の研究でTGF-β/BMPシグナルとその下流因子であるSLC14A1やPEG10の発現が軟骨肉腫の悪性度に関与し、さらにPEG10については細胞増殖や運動、浸潤能とも関与していることが明らかとなった。今後、PEG10は軟骨肉腫における鑑別マーカーだけでなく分子治療標的となりうる可能性がある。
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