場所：京都工芸繊維大学 2号館4階441号室 （応用生物学専攻 大学院演習室）
Jamboor K. Vishwanatha, PhD
Regents Professor and Vice President
University of North Texas Health Science Center
Fort Worth, Texas, USA
Exosome mediated premetastatic niche formation in breast cancer
Tumor-derived exosomes are emerging mediators of tumorigenesis and tissue-specific metastasis. Proteomic profiling has identified Annexin A2 as one of the most highly expressed proteins in the exosomes; however, studies focused on the biological role of exosomal-AnnexinA2 (exo-AnxA2) are still lacking. We have characterized exo-AnxA2 and determined its function in angiogenesis and breast cancer metastasis. We used multiple in vitro and in vivo techniques to study the role of exo-AnxA2 in angiogenesis. Using atomic force microscopy and Western blotting, we characterized exo-AnxA2 expression in normal and breast cancer cells. In addition, using organ specific metastatic breast cancer cells and animal models we studied the role exo-AnxA2 in breast cancer metastasis. Results showed that exo-AnxA2 expression is significantly higher in malignant cells than normal and pre-metastatic breast cancer cells. In vitro and in vivo studies showed that exo-AnxA2 promotes tPA-dependent angiogenesis. In vivo studies showed that metastatic exosomes create a favorable microenvironment for metastasis and exo-AnxA2 plays an important role in this process, since priming with AnxA2-depleted exosomes reduces brain (~4-fold) and lung (~2-fold) metastasis. Upon delineating the mechanism we discovered that exo-AnxA2 causes macrophage-mediated activation of the p38MAPK, NF-κB, and STAT3 pathways and increased secretion of IL-6 and TNF-alpha. These data demonstrate an important role for exo-AnxA2 in breast cancer pathogenesis.