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Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts
被引:24
作者:
Rezaei, Maryam
[1
]
Cavaco, Ana C. Martins
[1
,2
]
Stehling, Martin
[3
]
Nottebaum, Astrid
[4
]
Brockhaus, Katrin
[1
]
Caliandro, Michele F.
[1
]
Schelhaas, Sonja
[5
]
Schmalbein, Felix
[1
]
Vestweber, Dietmar
[4
]
Eble, Johannes A.
[1
]
机构:
[1] Univ Munster, Inst Physiol Chem & Pathobiochem, D-48149 Munster, Germany
[2] Univ Lisbon, Inst Med Mol, Luis Costa Lab, Fac Med, P-1649028 Lisbon, Portugal
[3] Max Planck Inst Mol Biomed, Dept Cell & Dev Biol, Flow Cytometry Unit, D-48149 Munster, Germany
[4] Max Planck Inst Mol Biomed, Dept Vasc Cell Biol, D-48149 Munster, Germany
[5] Univ Munster, European Inst Mol Imaging EIMI, D-48149 Munster, Germany
来源:
关键词:
breast cancer;
human umbilical vein endothelial cells (HUVEC);
epithelial-mesenchymal transition (EMT);
cadherin switching;
extracellular vesicles (EVs);
invasion;
vascular mimicry (VM);
MESENCHYMAL TRANSITION;
N-CADHERIN;
EPITHELIUM;
RELEVANCE;
JUNCTIONS;
DYNAMICS;
INVASION;
TUMORS;
D O I:
10.3390/cancers12082138
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Cadherins mediate cohesive contacts between isotypic cells by homophilic interaction and prevent contact between heterotypic cells. Breast cancer cells neighboring endothelial cells (ECs) atypically express vascular endothelial (VE)-cadherin. To understand this EC-induced VE-cadherin expression in breast cancer cells, MCF7 and MDA-MB-231 cells expressing different endogenous cadherins were co-cultured with ECs and analyzed for VE-cadherin at the transcriptional level and by confocal microscopy, flow cytometry, and immunoblotting. After losing their endogenous cadherins and neo-expression of VE-cadherin, these cells integrated into an EC monolayer without compromising the barrier function instantly. However, they induced the death of nearby ECs. EC-derived extracellular vesicles (EVs) contained soluble and membrane-anchored forms of VE-cadherin. Only the latter was re-utilized by the cancer cells. In a reporter gene assay, EC-adjacent cancer cells also showed a juxtacrine but no paracrine activation of the endogenous VE-cadherin gene. This cadherin switch enabled intimate contact between cancer and endothelial cells in a chicken chorioallantoic membrane tumor model showing vasculogenic mimicry (VM). This EV-mediated, EC-induced cadherin switch in breast cancer cells and the neo-expression of VE-cadherin mechanistically explain the mutual communication in the tumor microenvironment. Hence, it may be a target to tackle VM, which is often found in breast cancers of poor prognosis.
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页码:1 / 25
页数:25
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