Castration-induced acceleration of bone metastasis in a murine model of castration-resistant prostate cancer

2015 Fiscal Year Final Research Report

• Project/Area Number: 25861409
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Akita University
• Principal Investigator: Takamitsu Inoue 秋田大学, 医学部, 講師 (60375243)
• Research Collaborator: TAKAYAMA Kouichiro 秋田大学, 大学院医学研究科, 大学院生
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 前立腺癌 / 骨転移 / 破骨細胞 / 骨粗鬆症 / ホルモン療法

Outline of Final Research Achievements

Androgen deprivation therapy (ADT) has several adverse effects, including a reduction in bone mineral density (BMD). Reportedly, ADT reduces BMD by stimulating receptor activator of nuclear factor kappa-B (RANK) signaling in osteoclasts. RANKL inhibitors have been shown to prevent bone metastases. However, the possibility of ADT-induced acceleration of bone metastasis in castration-resistant prostate cancer (CRPC) has not been examined. In this study, we show that ADT significantly accelerates the establishment of CRPC bone metastases, with a reduction in BMD in a murine model. These results suggest that ADT creates a suitable bone microenvironment for circulating CRPC cells to implant into the bone and establish new bone metastases at an accelerated rate. This study supports the idea that it is necessary to suppress osteoclasts from the time of ADT initiation in patients with high-risk non-metastatic prostate cancer to prevent the accelerated establishment of new bone metastases.

Free Research Field

泌尿器腫瘍学