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Inhibition of TGFBIp expression reduces lymphangiogenesis and tumor metastasis.

Title
 Inhibition of TGFBIp expression reduces lymphangiogenesis and tumor metastasis. 
Authors
 Y-S Maeng ; B Aguilar ; E K Kim ; S-I Choi 
Issue Date
2015
Journal Title
 Oncogene 
ISSN
 0950-9232 
Citation
 Oncogene, Vol.null(null) : null, 2015 
Abstract
Transforming growth factor-β-induced protein (TGFBIp) is an extracellular matrix protein that has a role in a wide range of pathological conditions. However, the role of TGFBIp signaling in lymphangiogenesis is poorly understood. The purpose of this study was therefore to analyze the effects of TGFBIp on lymphangiogenesis and determine whether TGFBIp-related lymphangiogenesis is important for the metastasis of tumor cells. TGFBIp increased adhesion, migration, and morphologic differentiation of human lymphatic endothelial cells (LECs), consistent with an increase in lymphatic vessel sprouting in a three-dimensional lymphatic ring assay. TGFBIp also induced phosphorylation of intracellular signaling molecules SRC, FAK, AKT, JNK and ERK. TGFBIp-induced lymphatic vessel sprouting was inhibited by addition of anti-integrin β3 antibody and pharmacologic inhibitors of FAK, AKT, JNK or ERK. TGFBIp increased both CCL21 expression in LECs, a chemokine that actively recruits tumor cells expressing the cognate chemokine receptors to lymphatic vessels and LEC permeability by inducing the dissociation of VE-cadherin junctions between LECs via the activation of SRC signaling. In vivo, inhibition of TGFBIp expression in SW620 cancer cells dramatically reduced tumor lymphangiogenesis and metastasis. Collectively, our findings demonstrate that TGFBIp is a lymphangiogenic factor contributing to tumor dissemination and represents a potential target to inhibit metastasis.Oncogene advance online publication, 16 March 2015; doi:10.1038/onc.2015.73.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/141848
DOI
10.1038/onc.2015.73
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Ophthalmology
1. 연구논문 > 5. Research Institutes > Corneal Dystrophy Research Institute
Yonsei Authors
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Link
 http://www.nature.com/onc/journal/vaop/ncurrent/full/onc201573a.html
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