Malignant T cells express lymphotoxin alpha and drive endothelial activation in cutaneous T cell lymphoma
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Malignant T cells express lymphotoxin alpha and drive endothelial activation in cutaneous T cell lymphoma. / Lauenborg, Britt; Christensen, Louise; Ralfkiaer, Ulrik; Kopp, Katharina Luise Maria; Jønson, Lars; Dabelsteen, Sally; Bonefeld, Charlotte M; Geisler, Carsten; Gjerdrum, Lise Mette R; Zhang, Qian; Wasik, Mariusz A; Ralfkiaer, Elisabeth; Ødum, Niels; Andersen, Anders Woetmann.
In: OncoTarget, Vol. 6, No. 17, 2015, p. 15235-15249.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Malignant T cells express lymphotoxin alpha 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
Y1 - 2015
N2 - 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.
AB - 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.
KW - CTCL
KW - LTA
KW - angiogenesis
U2 - 10.18632/oncotarget.3837
DO - 10.18632/oncotarget.3837
M3 - Journal article
C2 - 25915535
VL - 6
SP - 15235
EP - 15249
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 17
ER -
ID: 156561324