CD133 shapes extracellular vesicle cargo and angiogenic function in basal-like triple-negative breast cancer
Extracellular vesicles (EVs) are central mediators of tumor-stroma communication, yet the mechanisms governing their biogenesis and functional cargo remain poorly understood. Here, we identify CD133 (Prominin-1), selectively expressed in basal-like triple-negative breast cancer (BL-TNBC) cells, as a key regulator of EV production and cargo composition. CD133 localizes to plasma membrane protrusions and lipid rafts, maintaining membrane architecture, promoting EV release, and shaping selective protein loading, including the pro-angiogenic factor CD105. Functionally, CD133 EVs potently induce endothelial tubulogenesis in a CD105-dependent manner, independently of EV uptake or endothelial proliferation. In vivo, these EVs preferentially accumulate in the lung and liver, highlighting organ-specific communication. Mechanistically, CD133 maintains lipid raft integrity, facilitating CD105 selective incorporation into vesicles, thereby establishing a spatially coordinated CD133-CD105 axis. Together, our findings define a subtype-specific EV population whose identity and angiogenic activity are dictated by membrane organization. By linking protrusion architecture to vesicle-mediated signaling, this study highlights CD133-enriched EVs as potential biomarkers and therapeutic targets in aggressive BL-TNBC.