| Project/Area Number |
19K18964
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57020:Oral pathobiological science-related
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 口腔癌 / 悪性腫瘍 / 転移 / TPM1 / プロテオーム解析 / SiRNA / 口腔扁平上皮癌 |
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| Outline of Research at the Start |
癌の浸潤・転移抑制が可能となれば、身体に非可逆的ダメージを与えること無く、自立可能な最低限の身体機能が維持された長期の担癌状態が期待できる。背景因子が同一の単一腫瘍細胞由来の性質の異なる２種類のクローン細胞(造腫瘍性と転移能の弱い細胞と高い細胞)を対象にしたプロテオミクスによる差次的発現解析で、Calreticulin(CARL)、Tropomyosin 1 alpha chain(TPM1)、Heat shock protein 90kDa beta family member 1(HSP90B1)の３種類のタンパク質に着目し、これらを標的として癌との共生につながる新規治療法の開発を目指す。
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| Outline of Final Research Achievements |
TPM1 expression of tissue samples obtained from 111 patients with OSCC was evaluated using immunohistochemistry. The associations between TPM1 expression, clinicopathological characteristics and patient survival were also analyzed. In addition, the role of TPM1 in cancer cell invasion and metastasis was examined by transfecting TPM1-siRNA into HSC2 and HSC4. Immunohistochemical analysis revealed that tissue samples of 70.2% of the OSCC patients were high expression for TPM1. In addition, TPM1 expression status was correlated with the T classification (P=0.0006), N classification (P=0.0004), stage (P=0.0007) and overall survival (P=0.0178). In vitro studies indicated that the suppression of TPM1 by TPM1-siRNA increased cancer cell proliferative, wound healing and migratory abilities. These findings suggest that low expression levels of TPM1 may contribute to cancer prognosis, and that TPM1 may have potential as a prognostic factor for patients with OSCC.
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| Academic Significance and Societal Importance of the Research Achievements |
TPM1の低発現は口腔扁平上皮癌の浸潤・転移能獲得において重要な役割を演じるとともに、有用な予後因子となり得る可能性が示唆された。TPM1は、アクチンフィラメントと結合し、フィラメントの安定化や他の結合タンパク質との結合を調節する作用を有する。このTPM1発現を制御することで予後の向上が期待できるため、TPM1発現を増強できる併用薬の探索や、TPM1そのものを標的とし、その発現を増強させるような治療法の開発により、口腔扁平上皮癌患者の治療成績はさらに向上することが期待される。
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