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

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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.

Original languageEnglish
JournalOncotarget
Volume6
Issue number17
Pages (from-to)15235-49
Number of pages15
ISSN1949-2553
Publication statusPublished - 20 Jun 2015

Bibliographical note

Lauenborg B1, Christensen L1, Ralfkiaer U2, Kopp KL1, Jønson L3, Dabelsteen S4, Bonefeld CM1, Geisler C1, Gjerdrum LM5, Zhang Q6, Wasik MA6, Ralfkiaer E7, Ødum N1, Woetmann A1.
Author information
1Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
2Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark.
3Center for Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
4Department of Oral Medicine and Pathology, School of Dentistry, University of Copenhagen, Copenhagen, Denmark.
5Department of Pathology, Roskilde Hospital, Roskilde, Denmark.
6Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
7Department of Pathology, Copenhagen University Hospital, Copenhagen, Denmark.

ID: 45731609