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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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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. |
format | Online Article Text |
id | pubmed-4558148 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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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