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

Britt Lauenborg; Louise Christensen; Ulrik Ralfkiaer; Katharina Luise Maria Kopp; Lars Jønson; Sally Dabelsteen; Charlotte M Bonefeld; Carsten Geisler; Lise Mette R Gjerdrum; Qian Zhang; Mariusz A Wasik; Elisabeth Ralfkiaer; Niels Ødum; Anders Woetmann Andersen

doi:10.18632/oncotarget.3837

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

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

Abstract

Lymphotoxin a (LTa) 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 LTa in situ and that LTa expression is driven by aberrantly activated JAK3/STAT5 pathway. Importantly, via TNF receptor 2, LTa functions as an autocrine factor by stimulating expression of IL-6 in the malignant cells. LTa and IL-6, together with VEGF promote angiogenesis by inducing endothelial cell sprouting and tube formation. Thus, we propose that LTa plays a role in malignant angiogenesis and disease progression in CTCL and may serve as a therapeutic target in this disease.

Original language	English
Journal	OncoTarget
Volume	6
Issue number	17
Pages (from-to)	15235-49
Number of pages	15
ISSN	1949-2553
DOIs	https://doi.org/10.18632/oncotarget.3837
Publication status	Published - 20 Jun 2015

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Lauenborg, B., Christensen, L., Ralfkiaer, U., Kopp, K. L. M., Jønson, L., Dabelsteen, S., Bonefeld, C. M., Geisler, C., Gjerdrum, L. M. R., Zhang, Q., Wasik, M. A., Ralfkiaer, E., Ødum, N., & Andersen, A. W. (2015). Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma. OncoTarget, 6(17), 15235-49. https://doi.org/10.18632/oncotarget.3837

Lauenborg, B, Christensen, L, Ralfkiaer, U, Kopp, KLM, Jønson, L, Dabelsteen, S, Bonefeld, CM, Geisler, C , Gjerdrum, LMR, Zhang, Q, Wasik, MA, Ralfkiaer, E, Ødum, N & Andersen, AW 2015, 'Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma', OncoTarget, vol. 6, no. 17, pp. 15235-49. https://doi.org/10.18632/oncotarget.3837

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title = "Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma",

abstract = "Lymphotoxin a (LTa) 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 LTa in situ and that LTa expression is driven by aberrantly activated JAK3/STAT5 pathway. Importantly, via TNF receptor 2, LTa functions as an autocrine factor by stimulating expression of IL-6 in the malignant cells. LTa and IL-6, together with VEGF promote angiogenesis by inducing endothelial cell sprouting and tube formation. Thus, we propose that LTa plays a role in malignant angiogenesis and disease progression in CTCL and may serve as a therapeutic target in this disease.",

author = "Britt Lauenborg and Louise Christensen and Ulrik Ralfkiaer and Kopp, {Katharina Luise Maria} and Lars J{\o}nson and Sally Dabelsteen and Bonefeld, {Charlotte M} and Carsten Geisler and Gjerdrum, {Lise Mette R} and Qian Zhang and Wasik, {Mariusz A} and Elisabeth Ralfkiaer and Niels {\O}dum and Andersen, {Anders Woetmann}",

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doi = "10.18632/oncotarget.3837",

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TY - JOUR

T1 - Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma

AU - Lauenborg, Britt

AU - Christensen, Louise

AU - Ralfkiaer, Ulrik

AU - Kopp, Katharina Luise Maria

AU - Jønson, Lars

AU - Dabelsteen, Sally

AU - Bonefeld, Charlotte M

AU - Geisler, Carsten

AU - Gjerdrum, Lise Mette R

AU - Zhang, Qian

AU - Wasik, Mariusz A

AU - Ralfkiaer, Elisabeth

AU - Ødum, Niels

AU - Andersen, Anders Woetmann

PY - 2015/6/20

Y1 - 2015/6/20

N2 - Lymphotoxin a (LTa) 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 LTa in situ and that LTa expression is driven by aberrantly activated JAK3/STAT5 pathway. Importantly, via TNF receptor 2, LTa functions as an autocrine factor by stimulating expression of IL-6 in the malignant cells. LTa and IL-6, together with VEGF promote angiogenesis by inducing endothelial cell sprouting and tube formation. Thus, we propose that LTa plays a role in malignant angiogenesis and disease progression in CTCL and may serve as a therapeutic target in this disease.

AB - Lymphotoxin a (LTa) 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 LTa in situ and that LTa expression is driven by aberrantly activated JAK3/STAT5 pathway. Importantly, via TNF receptor 2, LTa functions as an autocrine factor by stimulating expression of IL-6 in the malignant cells. LTa and IL-6, together with VEGF promote angiogenesis by inducing endothelial cell sprouting and tube formation. Thus, we propose that LTa plays a role in malignant angiogenesis and disease progression in CTCL and may serve as a therapeutic target in this disease.

U2 - 10.18632/oncotarget.3837

DO - 10.18632/oncotarget.3837

M3 - Journal article

C2 - 25915535

SN - 1949-2553

VL - 6

SP - 15235

EP - 15249

JO - OncoTarget

JF - OncoTarget

IS - 17

ER -

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

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