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, Alice S.T. Wong

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Article number2270
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

Fingerprint

Exosomes
angiogenesis
Cadherins
Tumors
tumors
cancer
Ovarian Neoplasms
Neoplasms
prognosis
biomarkers
Ascites
therapy
routes
activation
Catenins
Angiogenesis Inducing Agents
Endothelial cells
Biomarkers
Endothelial Cells
Chemical activation

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Soluble E-cadherin promotes tumor angiogenesis and localizes to exosome surface. / Tang, Maggie K.S.; Yue, Patrick Y.K.; Ip, Philip P.; Huang, Rui Lan; Lai, Hung Cheng; Cheung, Annie N.Y.; Tse, Ka Yu; Ngan, Hextan Y.S.; Wong, Alice S.T.

In: Nature Communications, Vol. 9, No. 1, 2270, 01.12.2018.

Research output: Contribution to journalArticle

Tang, Maggie K.S. ; Yue, Patrick Y.K. ; Ip, Philip P. ; Huang, Rui Lan ; Lai, Hung Cheng ; Cheung, Annie N.Y. ; Tse, Ka Yu ; Ngan, Hextan Y.S. ; Wong, Alice S.T. / Soluble E-cadherin promotes tumor angiogenesis and localizes to exosome surface. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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