CD133 Shapes Extracellular Vesicle Cargo and Angiogenic Function in Basal-Like Triple-Negative Breast Cancer.

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Extracellular vesicles (EVs) mediate tumor-stroma communication, but their biogenesis and cargo mechanisms are unclear.
• Basal-like triple-negative breast cancer (BL-TNBC) is aggressive, necessitating novel therapeutic targets and biomarkers.

Purpose of the Study:

• To investigate the role of CD133 (Prominin-1) in EV production and function in BL-TNBC.
• To elucidate the mechanisms by which CD133 influences EV cargo and angiogenic activity.

Main Methods:

• Immunofluorescence microscopy to localize CD133 within cancer cells.
• EV isolation and characterization.
• In vitro endothelial tubulogenesis assays.
• In vivo biodistribution studies.

Main Results:

• CD133 localizes to membrane protrusions and lipid rafts, organizing EV release and cargo loading.
• CD133+ EVs selectively package the pro-angiogenic factor CD105.
• CD133+ EVs potently induce endothelial tubulogenesis via a CD105-dependent mechanism.
• In vivo, these EVs preferentially accumulate in the lung and liver.

Conclusions:

• CD133 is a key regulator of EV biogenesis and cargo in BL-TNBC, establishing a CD133-CD105 axis.
• CD133+ EVs exhibit specific angiogenic potential and organ tropism.
• CD133-enriched EVs represent potential biomarkers and therapeutic targets for aggressive BL-TNBC.