Progression of prostate cancer bone metastasis by exosomal micro RNA regulated-chemokine

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11126
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: St. Luke's International University
• Principal Investigator: NARIMOTO Kazutaka 聖路加国際大学, 聖路加国際病院, 医幹 (50645207)
• Co-Investigator(Kenkyū-buntansha): 溝上 敦 金沢大学, 医学系, 教授 (50248580) ; 泉 浩二 金沢大学, 附属病院, 講師 (80646787)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 前立腺癌 / 腫瘍免疫

Outline of Final Research Achievements

The cell-cell interaction between bone stromal cells and prostate cancer cells produced CCL5 which in turn increased migration abiliy of prostate cancer cells. Immunohistochemistry revealed CCR5, a receptor of CCL5, expressed in prostate cancer tissue stronger than normal prostate tissue. Coffee ingredients, cafestol and kahweol, synergistically inhibited both proliferation and migration ability of prostate cancer cells in a dose dependent manner. Cafestol and kahweol inhibited the expression of androgen receptor and its nuclear translocation, and also inhibited CCR5 expression in prostate cancer cells. In prostate cancer bone metastasis, CCL5-CCR5 signaling may increase the metastatic ability of prostate cencer cells and cafestol and kahweol have a potential ability to inhibit prostate cancer metastasis via inhibition of CCL5-CCR5 signaling.

Free Research Field

泌尿器腫瘍学

Academic Significance and Societal Importance of the Research Achievements

骨転移が多い前立腺癌における骨から骨への転移促進機構は未だ未解明であったが、本研究により、骨転移巣でのCCL5-CCR5経路の活性化が、前立腺癌細胞の転移能を亢進させ、さらなる骨転移を誘発する可能性が示唆された。さらに、コーヒーの成分の中で、カーウェオールとカフェストールはCCL5-CCR5経路の抑制を介し、前立腺癌の転移を抑制できる可能性が示唆された。CCL5-CCR5経路が新規治療ターゲットとして明らかにされただけではなく、カーウェオールとカフェストールが前立腺癌治療薬となる潜在性も明らかになった。