Exosomal Annexin II Promotes Angiogenesis and Breast Cancer Metastasis

摘要: Tumor-derived exosomes are emerging mediators of tumorigenesis and tissue-specific metastasis. Proteomic profiling has identified Annexin II as one the most highly expressed proteins in exosomes; however, studies focused on biological role exosomal (exo-Anx II) still lacking. In this study, mechanistic insight was sought regarding exo-Anx its function angiogenesis breast cancer Multiple vitro vivo techniques were used to study angiogenesis. Using atomic force microscopy Western blotting, expression characterized normal cells. addition, organ-specific metastatic cells animal models define Results revealed that is significantly higher malignant than premetastatic demonstrated promotes tPA-dependent Furthermore, analysis indicated create a favorable microenvironment for metastasis, plays an important process, priming with Anx II-depleted reduces brain (∼4-fold) lung (∼2-fold) Upon delineating mechanism, it discovered causes macrophage-mediated activation p38MAPK, NF-κB, STAT3 pathways increased secretion IL6 TNFα. These data demonstrate pathogenesis. Implications: Exosome-associated which can be exploited potential biomarker well therapeutic target diagnosis treatment cancer. Mol Cancer Res; 15(1); 93–105. ©2016 AACR.