Sawada Yuichiro, Kikugawa Tadahiko, Onishi Tomoya, Arai Osuke, Iio Hiroyuki, Miura Noriyoshi, Yoshida Shuhei, Ikedo Aoi, Yanagihara Yuta, Saeki Noritaka, Sakakibara Iori, Győrffy Balázs, Kishida Takeshi, Okubo Yoichiro, Nakamura Yoshiyasu, Sato Shinya, Miyagi Yohei, Saika Takashi, Imai Yuuki
Department of Urology, Ehime University Graduate School of Medicine, Toon, Japan.
Department of Pathophysiology, Ehime University Graduate School of Medicine, Toon, Japan.
Int J Cancer. 2025 Dec 1;157(11):2399-2412. doi: 10.1002/ijc.70012. Epub 2025 Jun 21.
Prostate cancer causes a high frequency of bone metastases. The purpose of this study was to identify molecules that regulate prostate cancer bone metastasis as potential therapeutic and/or prognostic targets in prostate cancer, using integrative genome-wide data. Based on the biological characterization of prostate cancer cell lines and integrated big data analysis of clinical samples, we identified CTHRC1 as a candidate gene that regulates prostate cancer bone metastasis. The knockdown of CTHRC1 suppressed cell migration and cell adhesion, but not cell proliferation, in vitro and in vivo. In a mouse tibia xenograft model, CTHRC1 knockdown markedly suppressed metastatic growth of prostate cancer cells in the bone microenvironment. CTHRC1 also promoted in vitro osteoclast differentiation. The analysis of 343 human prostate cancer biopsy samples showed that CTHRC1 expression was positively correlated with bone metastasis, indicating that CTHRC1 could be a useful predictive marker for bone metastasis. Our findings illustrate the clinical relevance of CTHRC1 and demonstrate that CTHRC1 plays an important role in prostate cancer bone metastasis. CTHRC1 may be useful for predicting prostate cancer bone metastasis and may lead to the development of new methods for the prevention and treatment of metastasis.
前列腺癌会导致高频率的骨转移。本研究的目的是利用全基因组综合数据,确定在前列腺癌中作为潜在治疗和/或预后靶点调节前列腺癌骨转移的分子。基于前列腺癌细胞系的生物学特性以及临床样本的综合大数据分析,我们确定CTHRC1为调节前列腺癌骨转移的候选基因。在体外和体内,敲低CTHRC1可抑制细胞迁移和细胞黏附,但不影响细胞增殖。在小鼠胫骨异种移植模型中,敲低CTHRC1可显著抑制前列腺癌细胞在骨微环境中的转移生长。CTHRC1还促进体外破骨细胞分化。对343例人类前列腺癌活检样本的分析表明,CTHRC1表达与骨转移呈正相关,表明CTHRC1可能是骨转移的有用预测标志物。我们的研究结果阐明了CTHRC1的临床相关性,并证明CTHRC1在前列腺癌骨转移中起重要作用。CTHRC1可能有助于预测前列腺癌骨转移,并可能导致开发预防和治疗转移的新方法。