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Thrombospondin type I domain containing 7A (THSD7A) mediates endothelial cell migration and tube formation
Author(s) -
Wang ChiehHuei,
Su PeiTsu,
Du XiaoYan,
Kuo MengWei,
Lin ChiaYi,
Yang ChungChi,
Chan HauShien,
Chang ShingJyh,
Kuo Calvin,
Seo Kyunga,
Leung Lawrence L.,
Chuang YungJen
Publication year - 2010
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21990
Subject(s) - thrombospondin , microbiology and biotechnology , umbilical vein , cell migration , angiogenesis , cytoskeleton , paxillin , focal adhesion , endothelial stem cell , thrombospondin 1 , biology , human umbilical vein endothelial cell , chemistry , cell , signal transduction , biochemistry , genetics , metalloproteinase , in vitro , matrix metalloproteinase
Angiogenesis is a highly organized process controlled by a series of molecular events. While much effort has been devoted to identifying angiogenic factors and their reciprocal receptors, far less information is available on the molecular mechanisms underlying directed endothelial cell migration. To search for novel proteins that participate in this process, we used the serial analysis of gene expression (SAGE) transcript profiling approach to identify genes that are selectively expressed in endothelial cells (ECs). Two EC SAGE libraries were constructed from human umbilical vein and artery ECs to enable data‐mining against other non‐ECs. A novel endothelial protein, Thrombospondin Type I Domain Containing 7A (THSD7A), with preferential expression in placenta vasculature and in human umbilical vein endothelial cells (HUVECs) was identified and targeted for further characterization. Overexpression of a THSD7A carboxyl‐terminal fragment in HUVECs inhibited cell migration and disrupted tube formation, while suppression of THSD7A expression enhanced HUVEC migration and tube formation. Immunohistological analysis revealed that THSD7A was expressed at the leading edge of migrating HUVECs, and it co‐localized with α V β 3 integrin and paxillin. This distribution was dispersed from focal adhesions after disruption of the actin cytoskeleton, suggesting the involvement of THSD7A in cytoskeletal organization. Our results show that THSD7A is a novel placenta endothelial protein that mediates EC migration and tube formation, and they highlight its potential as a new target for anti‐angiogenic therapy. J. Cell. Physiol. 222: 685–694, 2010. © 2009 Wiley‐Liss, Inc.