昆虫バイオメディカル研究セミナー

 

日時2017526(金)   午後430分〜530

場所京都工芸繊維大学 2号館4441号室  応用生物学専攻 大学院演習室

講演者:

Jamboor K. Vishwanatha, PhD

Regents Professor and Vice President

University of North Texas Health Science Center

 Fort Worth, Texas, USA

 

講演要旨

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.

 

 

 

連絡先:昆虫先端研究推進センター 山口政光(075-724-7781