Exosomal annexin II promotes angiogenesis and breast cancer metastasis

Sayantan Maji, Pankaj Chaudhary, Irina Akopova, Phung M. Nguyen, Richard J. Hare, Ignacy Gryczynski, Jamboor K. Vishwanatha

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)93-105
Number of pages13
JournalMolecular Cancer Research
Volume15
Issue number1
DOIs
StatePublished - 1 Jan 2017

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Annexin A2
Breast Neoplasms
Neoplasm Metastasis
Exosomes
Atomic Force Microscopy
Secretory Pathway
Proteomics

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Maji, Sayantan ; Chaudhary, Pankaj ; Akopova, Irina ; Nguyen, Phung M. ; Hare, Richard J. ; Gryczynski, Ignacy ; Vishwanatha, Jamboor K. / Exosomal annexin II promotes angiogenesis and breast cancer metastasis. In: Molecular Cancer Research. 2017 ; Vol. 15, No. 1. pp. 93-105.
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Exosomal annexin II promotes angiogenesis and breast cancer metastasis. / Maji, Sayantan; Chaudhary, Pankaj; Akopova, Irina; Nguyen, Phung M.; Hare, Richard J.; Gryczynski, Ignacy; Vishwanatha, Jamboor K.

In: Molecular Cancer Research, Vol. 15, No. 1, 01.01.2017, p. 93-105.

Research output: Contribution to journalArticle

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