Soluble E-cadherin promotes tumor angiogenesis and localizes to exosome surface

Maggie K. S. Tang, Patrick Y. K. Yue, Philip P. Ip, Rui-Lan Huang, Hung-Cheng Lai, Annie N. Y. Cheung, Ka Yu Tse, Hextan Y. S. Ngan and Alice S. T. Wong ()
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Maggie K. S. Tang: University of Hong Kong
Patrick Y. K. Yue: Hong Kong Baptist University
Philip P. Ip: University of Hong Kong
Rui-Lan Huang: Taipei Medical University
Hung-Cheng Lai: Taipei Medical University
Annie N. Y. Cheung: University of Hong Kong
Ka Yu Tse: University of Hong Kong
Hextan Y. S. Ngan: University of Hong Kong
Alice S. T. Wong: University of Hong Kong

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract The limitations of current anti-angiogenic therapies necessitate other targets with complimentary mechanisms. Here, we show for the first time that soluble E-cadherin (sE-cad) (an 80-kDa soluble form), which is highly expressed in the malignant ascites of ovarian cancer patients, is a potent inducer of angiogenesis. In addition to ectodomain shedding, we provide further evidence that sE-cad is abundantly released in the form of exosomes. Mechanistically, sE-cad-positive exosomes heterodimerize with VE-cadherin on endothelial cells and transduce a novel sequential activation of β-catenin and NFκB signaling. In vivo and clinical data prove the relevance of sE-cad-positive exosomes for malignant ascites formation and widespread peritoneal dissemination. These data advance our understanding of the molecular regulation of angiogenesis in ovarian cancer and support the therapeutic potential of targeting sE-cad. The exosomal release of sE-cad, which represents a common route for externalization in ovarian cancer, could potentially be biomarkers for diagnosis and prognosis.

Date: 2018
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DOI: 10.1038/s41467-018-04695-7

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