Fig. 8. Proposed mechanism of exosomal miR-19a and IBSP mediated bone metastasis in ER⁺ breast cancer.

In the early metastatic niche, ER⁺ breast cancer cells secrete IBSP as a chemoattractant to recruit precursors of OC cells, creating an OC precursor-enriched microenvironment. OC precursors incorporate exosomes from breast cancer cells, and miR-19a is transported into OC precursors. Inside the OC precursors, miR-19a suppresses PTEN expression, activates NF-κB and AKT pathways, and promotes osteoclastogenesis. Mature OC cells induce bone resorption, liberating growth factors from the bone matrix, which further promote the growth of cancer cells.