The mechanism of AR signaling-independent prostate cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19558
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Mizokami Atsushi 金沢大学, 医学系, 教授 (50248580)
• Co-Investigator(Kenkyū-buntansha): 泉 浩二 金沢大学, 附属病院, 講師 (80646787)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 去勢抵抗性前立腺癌 / 肝転移 / 肝間質細胞 / 間葉上皮移行

Outline of Final Research Achievements

The increase in proliferation of C4-2B and LNCaP cells cocultured with Fa2N-4 cells was small, but the increase in migration of those cells were huge. Whereas, this migration increase of cancer cells was decreased by AR knockdown in Fa2N-4. In these coculture systems, midkine, CCL20, and CXCL12 secretions were increased in supernatant. In addtion, expression of CD44, which is an important molecule for cell-cell adhesion, was increased in taxane-resistant DU145 cells, suggesting that liver metastasized prostate canecr cells are tends to decrease their migration ability and show mesenchymal-epithelial transition under AR signal blockade status.

Free Research Field

泌尿器腫瘍学

Academic Significance and Societal Importance of the Research Achievements

強力な新世代AR標的薬が開発され、ARシグナルを究極的に抑制できるようになった結果、ARシグナルが増殖に全く関与しない新世代AR標的薬耐性前立腺癌細胞が生命予後を規定する時代が到来している。本研究の結果、ARシグナルに依存しない、タキサン耐性を有するような状態になった前立腺癌細胞は、肝転移を起こし、さらに定着する機構が存在する可能性が示された。本機構は進行前立腺癌に対する新たな治療ターゲットとなることが期待される。