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Microenvironmental interactions between endothelial and lymphoma cells: a role for the canonical WNT pathway in Hodgkin lymphoma

Linke, F
Author Linke, F Clinic of Hematology and Medical Oncology, University Medical Centre of the Georg-August University of Göttingen, Göttingen, Germany
Harenberg, M
Author Harenberg, M Clinic of Hematology and Medical Oncology, University Medical Centre of the Georg-August University of Göttingen, Göttingen, Germany
Nietert, M M
Author Nietert, M M Department of Medical Statistics, University Medical Centre of the Georg-August University of Göttingen, Göttingen, Germany
Zaunig, S
Author Zaunig, S Clinic of Hematology and Medical Oncology, University Medical Centre of the Georg-August University of Göttingen, Göttingen, Germany
von Bonin, F
Author von Bonin, F Clinic of Hematology and Medical Oncology, University Medical Centre of the Georg-August University of Göttingen, Göttingen, Germany
Arlt, A
Author Arlt, A Clinic of Hematology and Medical Oncology, University Medical Centre of the Georg-August University of Göttingen, Göttingen, Germany
Szczepanowski, M
Author Szczepanowski, M Section Hematopathology, UKSH Campus Kiel, Kiel, Germany
Weich, H A
Author Weich, H A Department of Chemical Biology, Helmholtz-Centre for Infection Research HZI, Braunschweig, Germany
Lutz, S
Author Lutz, S Institute of Pharmacology, University Medical Centre of the Georg-August University of Göttingen, Göttingen, Germany
Dullin, C
Author Dullin, C ORCID Institute of Diagnostic and Interventional Radiology, University Medical Centre of the Georg-August University of Göttingen, Göttingen, Germany
Janovská, P
Author Janovská, P Faculty of Science, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic
Krafčíková, M
Author Krafčíková, M Central European Institute of Technology, Masaryk University, Brno, Czech Republic
Trantírek, L
Author Trantírek, L Central European Institute of Technology, Masaryk University, Brno, Czech Republic
Ovesná, P
Author Ovesná, P Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic
Klapper, W
Author Klapper, W Section Hematopathology, UKSH Campus Kiel, Kiel, Germany
Beissbarth, T
Author Beissbarth, T Department of Medical Statistics, University Medical Centre of the Georg-August University of Göttingen, Göttingen, Germany
Alves, F
Author Alves, F Clinic of Hematology and Medical Oncology, University Medical Centre of the Georg-August University of Göttingen, Göttingen, Germany Institute of Diagnostic and Interventional Radiology, University Medical Centre of the Georg-August University of Göttingen, Göttingen, Germany Department of Molecular Biology of Neuronal Signals, Max Planck Institute for Experimental Medicine, Göttingen, Germany
Bryja, V
Author Bryja, V Faculty of Science, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of Czech Republic, Brno, Czech Republic
Trümper, L
Author Trümper, L Clinic of Hematology and Medical Oncology, University Medical Centre of the Georg-August University of Göttingen, Göttingen, Germany
Wilting, J
Author Wilting, J Department of Anatomy and Cell Biology, University Medical Centre of the Georg-August University of Göttingen, Göttingen, Germany
Kube, D
Author Kube, D Clinic of Hematology and Medical Oncology, University Medical Centre of the Georg-August University of Göttingen, Göttingen, Germany

Leukemia. 2017 Feb ; 31 (2) : 361-372. [epub] 20160818

ISSN 1476-5551 | 0887-6924
Source

Language English Country Great Britain, England Media print-electronic

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link https://www.medvik.cz/link/pmid27535218

PubMed 27535218
DOI 10.1038/leu.2016.232
PII: leu2016232
Knihovny.cz E-resources

MeSH
beta Catenin genetics metabolism MeSH
Cell Adhesion genetics MeSH
Cell Line MeSH
Chemokine CCL19 metabolism MeSH
Chemotaxis genetics immunology MeSH
Endothelial Cells metabolism MeSH
Hodgkin Disease genetics immunology metabolism pathology MeSH
Humans MeSH
Cell Communication * MeSH
Tumor Microenvironment * genetics immunology MeSH
Neovascularization, Pathologic MeSH
Cell Movement genetics MeSH
Wnt Signaling Pathway * MeSH
Lymphoid Enhancer-Binding Factor 1 genetics metabolism MeSH
Vascular Endothelial Growth Factor A metabolism MeSH
Check Tag
Humans MeSH
Publication type
Journal Article MeSH
Research Support, Non-U.S. Gov't MeSH
Names of Substances
beta Catenin MeSH
Chemokine CCL19 MeSH
Lymphoid Enhancer-Binding Factor 1 MeSH
Vascular Endothelial Growth Factor A MeSH

The interaction between vascular endothelial cells (ECs) and cancer cells is of vital importance to understand tumor dissemination. A paradigmatic cancer to study cell-cell interactions is classical Hodgkin Lymphoma (cHL) owing to its complex microenvironment. The role of the interplay between cHL and ECs remains poorly understood. Here we identify canonical WNT pathway activity as important for the mutual interactions between cHL cells and ECs. We demonstrate that local canonical WNT signaling activates cHL cell chemotaxis toward ECs, adhesion to EC layers and cell invasion using not only the Wnt-inhibitor Dickkopf, tankyrases and casein kinase 1 inhibitors but also knockdown of the lymphocyte enhancer binding-factor 1 (LEF-1) and β-catenin in cHL cells. Furthermore, LEF-1- and β-catenin-regulated cHL secretome promoted EC migration, sprouting and vascular tube formation involving vascular endothelial growth factor A (VEGF-A). Importantly, high VEGFA expression is associated with a worse overall survival of cHL patients. These findings strongly support the concept that WNTs might function as a regulator of lymphoma dissemination by affecting cHL cell chemotaxis and promoting EC behavior and thus angiogenesis through paracrine interactions.

Central European Institute of Technology Masaryk University Brno Czech Republic

Clinic of Hematology and Medical Oncology University Medical Centre of the Georg August University of Göttingen Göttingen Germany

Department of Anatomy and Cell Biology University Medical Centre of the Georg August University of Göttingen Göttingen Germany

Department of Chemical Biology Helmholtz Centre for Infection Research HZI Braunschweig Germany

Department of Cytokinetics Institute of Biophysics Academy of Sciences of Czech Republic Brno Czech Republic

Department of Medical Statistics University Medical Centre of the Georg August University of Göttingen Göttingen Germany

Department of Molecular Biology of Neuronal Signals Max Planck Institute for Experimental Medicine Göttingen Germany

Faculty of Science Institute of Experimental Biology Masaryk University Brno Czech Republic

Institute of Biostatistics and Analyses Masaryk University Brno Czech Republic

Institute of Diagnostic and Interventional Radiology University Medical Centre of the Georg August University of Göttingen Göttingen Germany

Institute of Pharmacology University Medical Centre of the Georg August University of Göttingen Göttingen Germany

Section Hematopathology UKSH Campus Kiel Kiel Germany