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

Autor: Maggie K.S. Tang, Patrick Y K Yue, Alice S.T. Wong, Rui Lan Huang, Hung Cheng Lai, Hextan Y.S. Ngan, Ka Yu Tse, Annie N.Y. Cheung, Philip P.C. Ip
Rok vydání: 2018
Předmět:
0301 basic medicine
endocrine system diseases
Angiogenesis
General Physics and Astronomy
Mice
SCID
Exosomes
Neovascularization
Mice
angiogenesis
Mice
Inbred NOD
lcsh:Science
beta Catenin
Ovarian Neoplasms
Multidisciplinary
Neovascularization
Pathologic
biology
Chemistry
NF-kappa B
Cadherins
female genital diseases and pregnancy complications
Ectodomain
Female
medicine.symptom
Signal Transduction
endocrine system
Beta-catenin
Science
Neovascularization
Physiologic
soluble E-cadherin
Exosome
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Antigens
CD
Cell Line
Tumor
Biomarkers
Tumor
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
exosome
Cadherin
General Chemistry
β-catenin
Microreview
medicine.disease
Microvesicles
ovarian carcinoma
030104 developmental biology
Solubility
Cancer research
biology.protein
lcsh:Q
Ovarian cancer
NFκB
Zdroj: Nature Communications, Vol 9, Iss 1, Pp 1-15 (2018)
Cell Stress
ISSN: 2041-1723
Popis: A key to successful metastasis is the formation of new vasculature, known as angiogenesis. Therefore, it is of great interest to unravel the underlying molecular mechanisms of tumor angiogenesis. Cadherins are a major class of cell surface receptors. The loss of cadherins, especially E-cadherin, is a well-established marker for tumor metastasis. Loss of E-cadherin is also a defining characteristic of several carcinomas, such as lobular carcinoma of the breast, and de-differentiated endometrioid carcinoma of the endometrium and ovary, which are known to be associated with more aggressive tumor behavior. Although E-cadherin is synthesized as a transmembrane molecule, its extracellular domain can be enzymatically cleaved off and released as a soluble E-cadherin (sE-cad), and this accounts for the loss of E-cadherin function or expression that has been implicated in tumor progression and metastasis. Importantly, sE-cad is present at high levels in the serum and malignant ascites of ovarian carcinoma patients. Nevertheless, little is known about how this essential protein dictates metastasis. Hitherto, many studies have given attention only to the dominant negative role of the loss of E-cadherin in weakening cell-cell adhesion, however, it is not known if sE-cad has biological activity in itself. In addition, the release mechanism of sE-cad has remained elusive. Here we show for the first time that sE-cad is a pivotal regulator of angiogenesis. We further show that exosomes are a novel major platform for the cleavage and release of sE-cad in vitro, in vivo and in patients’ derived samples (Nat Commun, 9: 2270).
Databáze: OpenAIRE
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