Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma

Lymphotoxin α (LTα) plays a key role in the formation of lymphatic vasculature and secondary lymphoid structures. Cutaneous T cell lymphoma (CTCL) is the most common primary lymphoma of the skin and in advanced stages, malignant T cells spreads through the lymphatic to regional lymph nodes to intern...

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Autores principales: Lauenborg, Britt, Christensen, Louise, Ralfkiaer, Ulrik, Kopp, Katharina L., Jønson, Lars, Dabelsteen, Sally, Bonefeld, Charlotte M., Geisler, Carsten, Gjerdrum, Lise Mette R., Zhang, Qian, Wasik, Mariusz A., Ralfkiaer, Elisabeth, Ødum, Niels, Woetmann, Anders
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558148/
https://www.ncbi.nlm.nih.gov/pubmed/25915535
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author Lauenborg, Britt
Christensen, Louise
Ralfkiaer, Ulrik
Kopp, Katharina L.
Jønson, Lars
Dabelsteen, Sally
Bonefeld, Charlotte M.
Geisler, Carsten
Gjerdrum, Lise Mette R.
Zhang, Qian
Wasik, Mariusz A.
Ralfkiaer, Elisabeth
Ødum, Niels
Woetmann, Anders
author_facet Lauenborg, Britt
Christensen, Louise
Ralfkiaer, Ulrik
Kopp, Katharina L.
Jønson, Lars
Dabelsteen, Sally
Bonefeld, Charlotte M.
Geisler, Carsten
Gjerdrum, Lise Mette R.
Zhang, Qian
Wasik, Mariusz A.
Ralfkiaer, Elisabeth
Ødum, Niels
Woetmann, Anders
author_sort Lauenborg, Britt
collection PubMed
description Lymphotoxin α (LTα) plays a key role in the formation of lymphatic vasculature and secondary lymphoid structures. Cutaneous T cell lymphoma (CTCL) is the most common primary lymphoma of the skin and in advanced stages, malignant T cells spreads through the lymphatic to regional lymph nodes to internal organs and blood. Yet, little is known about the mechanism of the CTCL dissemination. Here, we show that CTCL cells express LTα in situ and that LTα expression is driven by aberrantly activated JAK3/STAT5 pathway. Importantly, via TNF receptor 2, LTα functions as an autocrine factor by stimulating expression of IL-6 in the malignant cells. LTα and IL-6, together with VEGF promote angiogenesis by inducing endothelial cell sprouting and tube formation. Thus, we propose that LTα plays a role in malignant angiogenesis and disease progression in CTCL and may serve as a therapeutic target in this disease.
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spelling pubmed-45581482015-09-09 Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma Lauenborg, Britt Christensen, Louise Ralfkiaer, Ulrik Kopp, Katharina L. Jønson, Lars Dabelsteen, Sally Bonefeld, Charlotte M. Geisler, Carsten Gjerdrum, Lise Mette R. Zhang, Qian Wasik, Mariusz A. Ralfkiaer, Elisabeth Ødum, Niels Woetmann, Anders Oncotarget Research Paper Lymphotoxin α (LTα) plays a key role in the formation of lymphatic vasculature and secondary lymphoid structures. Cutaneous T cell lymphoma (CTCL) is the most common primary lymphoma of the skin and in advanced stages, malignant T cells spreads through the lymphatic to regional lymph nodes to internal organs and blood. Yet, little is known about the mechanism of the CTCL dissemination. Here, we show that CTCL cells express LTα in situ and that LTα expression is driven by aberrantly activated JAK3/STAT5 pathway. Importantly, via TNF receptor 2, LTα functions as an autocrine factor by stimulating expression of IL-6 in the malignant cells. LTα and IL-6, together with VEGF promote angiogenesis by inducing endothelial cell sprouting and tube formation. Thus, we propose that LTα plays a role in malignant angiogenesis and disease progression in CTCL and may serve as a therapeutic target in this disease. Impact Journals LLC 2015-04-15 /pmc/articles/PMC4558148/ /pubmed/25915535 Text en Copyright: © 2015 Lauenborg et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Lauenborg, Britt
Christensen, Louise
Ralfkiaer, Ulrik
Kopp, Katharina L.
Jønson, Lars
Dabelsteen, Sally
Bonefeld, Charlotte M.
Geisler, Carsten
Gjerdrum, Lise Mette R.
Zhang, Qian
Wasik, Mariusz A.
Ralfkiaer, Elisabeth
Ødum, Niels
Woetmann, Anders
Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma
title Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma
title_full Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma
title_fullStr Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma
title_full_unstemmed Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma
title_short Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma
title_sort malignant t cells express lymphotoxin α and drive endothelial activation in cutaneous t cell lymphoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558148/
https://www.ncbi.nlm.nih.gov/pubmed/25915535
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