Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
Laboratory of Integrative Oncology, National Cancer Center Research Institute, Tokyo, Japan.
J Extracell Vesicles. 2023 Mar;12(3):e12312. doi: 10.1002/jev2.12312.
Bone metastases are still incurable and result in the development of clinical complications and decreased survival for prostate cancer patients. Recently, a number of studies have shown that extracellular vesicles (EVs) play important roles in tumour progression. Here, we show that EVs from metastatic prostate cancer cells promote osteoclast formation in the presence of receptor activator of NF-κB ligand (RANKL). EV characterization followed by functional siRNA screening identified CUB-domain containing protein 1 (CDCP1), a transmembrane protein, as an inducer of osteoclastogenesis. Additionally, CDCP1 expression on plasma-derived EVs was upregulated in bone metastatic prostate cancer patients. Our findings elucidate the effect of EVs from metastatic prostate cancer cells on osteoclast formation, which is promoted by CDCP1 located on EVs. Furthermore, our data suggested that CDCP1 expression on EVs might be useful to detect bone metastasis of prostate cancer.
骨转移仍然无法治愈，导致前列腺癌患者出现临床并发症和生存时间缩短。最近，许多研究表明细胞外囊泡（EVs）在肿瘤进展中发挥重要作用。在这里，我们表明转移性前列腺癌细胞来源的 EVs 在核因子-κB 受体激活剂配体（RANKL）存在的情况下促进破骨细胞的形成。EV 特征分析和功能 siRNA 筛选鉴定出含 CUB 结构域蛋白 1（CDCP1），一种跨膜蛋白，是破骨细胞生成的诱导剂。此外，骨转移前列腺癌患者的血浆衍生 EVs 中 CDCP1 的表达上调。我们的研究结果阐明了转移性前列腺癌细胞来源的 EVs 对破骨细胞形成的影响，这种影响是由 EV 上的 CDCP1 介导的。此外，我们的数据表明，EV 上的 CDCP1 表达可能有助于检测前列腺癌的骨转移。
