Prostate Cancer Cell Extracellular Vesicles Increase Mineralisation of Bone Osteoblast Precursor Cells in an In Vitro Model

Skeletal metastases are the most common form of secondary tumour associated with prostate cancer (PCa). The aberrant function bone cells neighbouring these tumours leads to devel-opment osteoblastic lesions. Communication between PCa and in envi-ronments governs both formation/development lesion, growth tumour. Using osteoblasts as a model system, we observed that their conditioned medium could stimulate increase mineralisation osteoblasts’ differentiation. Secreted factors within PCa-conditioned responsible for changes included small extracellular vesicles (sEVs), which were sufficient drive osteoblastogenesis. MiR-seq, profiled miRNA content sEVs, showing miR-16-5p was highly ex-pressed. MiR-16 subsequently higher EV-treated 7F2 miR-16 mimic also mineralisation. Next, using RNA-seq vesicle (EV)-treated cells, large degree gene downregulation an increased Ingenuity® Pathway Analysis (IPA®) revealed (and other miRs) likely upstream effec-tor. MiR-16-5p targets possibly involved osteoblastogenesis, val-idation, namely AXIN2, PLSCR4, ADRB2 DLL1. We then confirmed targeting dow-regulation genes by sEV luciferase UTR (untranslated region) reporters. Conversely, overexpression DLL1 lead decreased osteoblastogene-sis. These results indicate is inducer osteoblastogenesis transmitted through cancer-derived sEVs. mechanism contributor towards for-mation lesions metastatic PCa.