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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4649-4656.
Prepublished online as a Blood First Edition Paper on February 10, 2005; DOI 10.1182/blood-2004-08-3382.
Previous Article | Next Article 
Submitted September 1, 2004
Accepted January 25, 2005
Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation
Tohru Morisada, Yuichi Oike*, Yoshihiro Yamada, Takashi Urano, Masaki Akao, Yoshiaki Kubota, Hiromitsu Maekawa, Yoshishige Kimura, Masako Ohmura, Takeshi Miyamoto, Shiro Nozawa, Gou Y Koh, Kari Alitalo, and Toshio Suda
Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo, Japan; Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan
Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo, Japan
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan
Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea, Republic of
Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
* Corresponding author; email: oike{at}sc.itc.keio.ac.jp.
Angiopoietin (Ang) signaling plays a role in angiogenesis and remodeling of blood vessels through the receptor tyrosine kinase Tie2, which is expressed on blood vessel endothelial cells (BECs). Recently it has been shown that Ang-2 is crucial for the formation of lymphatic vasculature and that defects in lymphangiogenesis seen in Ang-2 mutant mice are rescued by Ang-1. These findings suggest important roles for Ang signaling in the lymphatic vessel system, however, Ang function in lymphangiogenesis has not been characterized. In this study, we reveal that LYVE-1+ lymphatic endothelial cells (LECs) express Tie2 in both embryonic and adult settings, indicating that Ang signaling occurs in lymphatic vessels. Therefore, we examined whether Ang1 acts on in vivo lymphatic angiogenesis and in vitro growth of LECs. A chimeric form of Ang1, COMP-Ang1, promotes in vivo lymphatic angiogenesis in mouse cornea. Moreover, we found that COMP-Ang1 stimulates in vitro colony formation of LECs. These Ang-1-induced in vivo and in vitro effects on LECs were suppressed by soluble Tie2-Fc fusion protein, which acts as an inhibitor by sequestering Ang-1. On the basis of these observations, we propose that Ang signaling regulates lymphatic vessel formation through Tie2.

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