Project/Area Number |
17K16863
|
Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Obstetrics and gynecology
|
Research Institution | Wakayama Medical University |
Principal Investigator |
YAHATA TAMAKI 和歌山県立医科大学, 医学部, 客員研究員 (90647562)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
|
Keywords | 卵巣癌 / CRISPR/Cas9 / ケモカイン / PD-L1 / CXCR4 / CRISPR/Cas9 system / 婦人科学 |
Outline of Final Research Achievements |
The purpose of this study, we will develop a novel therapeutic strategy for ovarian cancer. We deplete the chemokine receptor gene involved in ovarian cancer progression using CRISPR/Cas9 system of genome editing technology, then, reveal its pathophysiological role in the cancer microenvironment. First, we the evaluated the expression of chemokine receptors in mouse ovarian cancer cell lines "ID8" using real time RT-PCR and flow cytometry, the expression of CCR5, CXCR4, and CX3CR1 were confirmed by real time RT-PCR, and the expression of CXCR4 was confirmed by flow cytometry. Second, we constructed gene modification vector of CCR5, CXCR4, CX3CR1, and transfected ID8 with the CXCR4 gene modification vector, the gene knockout cells were established. In the future, we plan to evaluate the involvement in ovarian cancer progression of these chemokines.
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Academic Significance and Societal Importance of the Research Achievements |
卵巣癌は女性の癌死因の半数を占める。進行症例に対する治療法は腫瘍減量手術と化学療法が主となるが、長期予後は不良であり、予後改善のためには新規標的治療の確立が必要である。本研究は卵巣癌進展に関与する分子としてケモカイン・ケモカイン受容体システムに注目し、マウス卵巣癌細胞株ID8のCCR5、CXCR4、CX3CR1のケモカイン受容体発現を確認した。ゲノム編集ツールであるCRISPR/Cas9システムを用いて、これらの遺伝子の発現を欠損させた細胞株を樹立し、癌微小環境下における病態生理学的役割を解明することで、卵巣癌において、ケモカインを標的とする新規治療法確立の基盤研究となる可能性がある。
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