Malignant T cells express lymphotoxin alpha 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)15235-15249
Number of pages15
ISSN1949-2553
DOIs
Publication statusPublished - 2015

    Research areas

  • CTCL, LTA, angiogenesis

ID: 156561324