Nab-paclitaxel inhibits angiogenesis via the CYR61/integrin αvβ3 Axis: Exosomal proteomics insights into breast cancer chemoprevention.

Albumin-bound paclitaxel (Nab-PTX), a nanoparticle albumin-bound formulation in which paclitaxel is conjugated to human serum albumin, has emerged as a pivotal agent in cancer therapy. Its significance stems not only from direct cytotoxic effects on cancer cells but also from multifaceted interactions with angiogenesis, a critical driver of tumor progression and metastasis. Nevertheless, the underlying mechanism of its anti-angiogenesis in breast cancer remains elusive. In the present study, we employed the iTRAQ (isobaric tags for relative and absolute quantification) technique to assess the effect of Nab-PTX on Triple-negative breast cancer cells (MDA-MB-231). A total of 5145 exosomal proteins were identified, of which 941 exhibited significant differences between Nab-PTX-treated cells and the control group (P-value<0.05). Notably, we found that CYR61 (Cysteine-rich angiogenic inducer 61), a secreted matricellular protein belonging to the CCN family, was significantly inhibited by Nab-PTX. Furthermore, our study demonstrated for the first time that Nab-PTX inhibits angiogenesis via the CYR61/Integrin αvβ3 signaling pathway. These findings elucidate a potential anti-angiogenesis mechanism of Nab-PTX and highlight CYR61's promise as a therapeutic target in human breast cancer.