| Project/Area Number |
18K16690
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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 56030:Urology-related
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| Research Institution | Mie University |
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Principal Investigator |
Sasaki Takeshi 三重大学, 医学部附属病院, 助教 (20644941)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 前立腺癌 / 癌関連線維芽細胞 / スプライシングバリアント / 線維芽細胞 / 去勢抵抗性前立腺癌 / 癌間質 |
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| Outline of Final Research Achievements |
Expression of androgen receptor (AR) splice variant (AR-V) has been identified as the mechanism associated with the development of castration-resistant prostate cancer (PCa). However, the mechanisms mediating increased expression of aberrant AR-Vs in PCa are still largely unknown.The purpose of this study was to identify if prostate fibroblasts in tumor stroma induces the expression of aberrant AR-Vs in PCa.We investigated the mRNA expression of AR, PSA, AR-V1, AR-V567es, AR-V7, and its target genes by co-cultured with three fibroblasts lines (PrSC, pcPrFs-M28, and pcPrFs-M31).mRNA expression of AR, AR-V1, and AR-V7 in LNCaP cells were increased by co-culture with pcPrFs-M28 but not with PrSC and pcPrFs-M31.Primary cultured prostate fibroblasts from prostate cancer specimens increased expression of aberrant AR-V1 and AR-V7 in PCa cells. Prostate fibroblasts in tumor stroma may be a target for the treatment preventing the expression of aberrant AR-Vs in PCa.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究結果から、前立腺癌間質の多様性に着目した、前立腺癌関連線維芽細胞(CAFs)由来パラクライン刺激による前立腺癌細胞のアンドロゲン受容体スプライシングバリアント(ARVs)発現修飾作用の可能性が示唆された。治療前のCAFsの性状解析を行い、CAFs由来ARVs発現誘導因子を阻害することで癌細胞のARVs発現上昇を阻止し、長期に治療奏効性を維持できる可能性が示された。これまでの画一的なホルモン治療と異なり、個々の患者に合わせ、癌間質をターゲットとした治療薬の併用というオーダーメイド医療の確立が期待される。
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