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
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.
引用
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页码:1 / 25
页数:25
相关论文
共 54 条
[1]   Exosomal HIF1α supports invasive potential of nasopharyngeal carcinoma-associated LMP1-positive exosomes [J].
Aga, M. ;
Bentz, G. L. ;
Raffa, S. ;
Torrisi, M. R. ;
Kondo, S. ;
Wakisaka, N. ;
Yoshizaki, T. ;
Pagano, J. S. ;
Shackelford, J. .
ONCOGENE, 2014, 33 (37) :4613-4622
[2]   EMT: 2016 [J].
Angela Nieto, M. ;
Huang, Ruby Yun-Ju ;
Jackson, Rebecca A. ;
Thiery, Jean Paul .
CELL, 2016, 166 (01) :21-45
[3]   E-cadherin induces mesenchymal-to-epithelial transition in human ovarian surface epithelium [J].
Auersperg, N ;
Pan, J ;
Grove, BD ;
Peterson, T ;
Fisher, J ;
Maines-Bandiera, S ;
Somasiri, A ;
Roskelley, CD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (11) :6249-6254
[4]   The classic cadherins in synaptic specificity [J].
Basu, Raunak ;
Taylor, Matthew R. ;
Williams, Megan E. .
CELL ADHESION & MIGRATION, 2015, 9 (03) :193-201
[5]   Homophilic and Heterophilic Interactions of Type II Cadherins Identify Specificity Groups Underlying Cell-Adhesive Behavior [J].
Brasch, Julia ;
Katsamba, Phinikoula S. ;
Harrison, Oliver J. ;
Ahlsen, Goran ;
Troyanovsky, Regina B. ;
Indra, Indrajyoti ;
Kaczynska, Anna ;
Kaeser, Benjamin ;
Troyanovsky, Sergey ;
Honig, Barry ;
Shapiro, Lawrence .
CELL REPORTS, 2018, 23 (06) :1840-1852
[6]   Epithelial to mesenchymal transition tumors: Fallacious or snail's pace? [J].
Cardiff, RD .
CLINICAL CANCER RESEARCH, 2005, 11 (24) :8534-8537
[7]   Collateral Damage IntendedCancer-Associated Fibroblasts and Vasculature Are Potential Targets in Cancer Therapy [J].
Cavaco, Ana ;
Rezaei, Maryam ;
Niland, Stephan ;
Eble, Johannes A. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2017, 18 (11)
[8]   The Interaction between Laminin-332 and α3β1 Integrin Determines Differentiation and Maintenance of CAFs, and Supports Invasion of Pancreatic Duct Adenocarcinoma Cells [J].
Cavaco, Ana C. Martins ;
Rezaei, Maryam ;
Caliandro, Michele F. ;
Lima, Augusto Martins ;
Stehling, Martin ;
Dhayat, Sameer A. ;
Haier, Joerg ;
Brakebusch, Cord ;
Eble, Johannes A. .
CANCERS, 2019, 11 (01)
[9]   Mosaic blood vessels in tumors: Frequency of cancer cells in contact with flowing blood [J].
Chang, YS ;
di Tomaso, E ;
McDonald, DM ;
Jones, R ;
Jain, RK ;
Munn, LL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (26) :14608-14613
[10]   The role of the cell-adhesion molecule E-cadherin as a tumour-suppressor gene [J].
Christofori, G ;
Semb, H .
TRENDS IN BIOCHEMICAL SCIENCES, 1999, 24 (02) :73-76