Oncotarget

Research Papers:

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

Britt Lauenborg, Louise Christensen, Ulrik Ralfkiaer, Katharina L. Kopp, Lars Jønson, Sally Dabelsteen, Charlotte M. Bonefeld, Carsten Geisler, Lise Mette R. Gjerdrum, Qian Zhang, Mariusz A. Wasik, Elisabeth Ralfkiaer, Niels Ødum and Anders Woetmann _

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Oncotarget. 2015; 6:15235-15249. https://doi.org/10.18632/oncotarget.3837

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Abstract

Britt Lauenborg1, Louise Christensen1, Ulrik Ralfkiaer2, Katharina L. Kopp1, Lars Jønson3, Sally Dabelsteen4, Charlotte M. Bonefeld1, Carsten Geisler1, Lise Mette R. Gjerdrum5, Qian Zhang6, Mariusz A. Wasik6, Elisabeth Ralfkiaer7, Niels Ødum1 and Anders Woetmann1

1 Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark

2 Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark

3 Center for Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark

4 Department of Oral Medicine and Pathology, School of Dentistry, University of Copenhagen, Copenhagen, Denmark

5 Department of Pathology, Roskilde Hospital, Roskilde, Denmark

6 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

7 Department of Pathology, Copenhagen University Hospital, Copenhagen, Denmark

Correspondence to:

Anders Woetmann, email:

Keywords: CTCL, LTA, angiogenesis

Received: August 16, 2014 Accepted: March 19, 2015 Published: April 15, 2015

Abstract

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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