Metastatic prostate cancer-derived extracellular vesicles facilitate osteoclastogenesis by transferring the CDCP1 protein

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-kappa B 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.

Automated summary

Bone metastases are a major concern for prostate cancer patients, leading to complications and decreased survival. Recent studies have found that extracellular vesicles (EVs) are involved in tumor progression. This study demonstrates that EVs from metastatic prostate cancer cells promote osteoclast formation, and the transmembrane protein CDCP1 is identified as an inducer of this process. Furthermore, CDCP1 expression on EVs may serve as a potential biomarker for detecting bone metastasis in prostate cancer.