TY - JOUR
T1 - Malignant T cells express lymphotoxin a and drive endothelial activation in cutaneous T cell lymphoma
AU - Lauenborg, Britt
AU - Christensen, Louise
AU - Ralfkiaer, Ulrik
AU - Kopp, Katharina L.
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 - Woetmann, Anders
PY - 2015/1/1
Y1 - 2015/1/1
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.
KW - Angiogenesis
KW - CTCL
KW - LTA
UR - http://www.scopus.com/inward/record.url?scp=84934343425&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.3837
DO - 10.18632/oncotarget.3837
M3 - Article
C2 - 25915535
AN - SCOPUS:84934343425
SN - 1949-2553
VL - 6
SP - 15235
EP - 15249
JO - Oncotarget
JF - Oncotarget
IS - 17
ER -