Exosomal and extracellular-vesicle miRNAs in prostate cancer-bone communication: mechanisms, biomarkers, and translational challenges

Abstract

Prostate cancer bone metastasis is increasingly understood as a dynamic interaction between disseminated tumor cells and a bone microenvironment that can be remodeled before, during, and after tumor-cell arrival. Extracellular vesicles (EVs), including preparations described as exosomes, may contribute to this communication by transferring proteins, lipids, and nucleic acids to bone-resident, stromal, and immune cells. Among these cargos, microRNAs (miRNAs) are attractive candidates because they can regulate multiple transcripts and cellular phenotypes. In this narrative review, we examine evidence linking EV-associated miRNAs to osteoclastogenesis, osteoblast-lineage remodeling, bone-marrow mesenchymal stromal-cell function, immune regulation, and reciprocal communication between bone-resident cells and prostate cancer cells. We distinguish evidence from pre-metastatic conditioning, metastatic colonization, and established metastatic growth, and we separate miRNA-specific causal evidence from associations or effects attributable to broader EV cargo. We also evaluate circulating EV-associated miRNAs as candidate biomarkers and discuss experimental therapeutic strategies, including inhibition of EV release, miRNA mimics or inhibitors, and engineered delivery systems. Current evidence supports a contributory role for EV-associated miRNAs in prostate cancer-bone communication, but the specificity of vesicle preparations, the causal contribution of individual miRNAs, and the existence of a bona fide bone pre-metastatic niche remain incompletely established. Standardized EV characterization, mechanistic validation, prospective clinical studies, and bone-targeted delivery systems are therefore required before these candidates can be translated into reliable biomarkers or therapies.