한빛사논문
Abstract
Young Jun Koh,1,2,9 Hak-Zoo Kim,1,2,9 Seong-Ik Hwang,1,3 Jeung Eun Lee,1,3 Nuri Oh,1,3 Keehoon Jung,1,2 Minah Kim,1,3 Kyung Eun Kim,1,2 Homin Kim,3 Nam-Kyu Lim,5 Choon-Ju Jeon,5 Gyun Min Lee,3,4 Byeong Hwa Jeon,6 Do-Hyun Nam,7 Hoon Ki Sung,8 Andras Nagy,8 Ook Joon Yoo,2 and Gou Young Koh1,2,3,4,7,*
1National Research Laboratory of Vascular Biology and Stem Cells
2Graduate School of Biomedical Science and Engineering
3Department of Biological Sciences
4Graduate School of Nanoscience and Technology
Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Korea
5Aprogen Inc., Daejeon, 305-701, Korea
6Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301-131, Korea
7Institute for Refractory Cancer Research Program, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710, Korea
8Department of Molecular Genetics, University of Toronto, Samuel Lunenfeld Research Institute, Mount Sinai Hospital,Ontario M5G 1X5, Canada
9These authors contributed equally to this study
*Correspondence
SUMMARY
Two vascular growth factor families, VEGF and the angiopoietins, play critical and coordinate roles in tumor progression and metastasis. A single inhibitor targeting both VEGF and angiopoietins is not available. Here, we developed a chimeric decoy receptor, namely double anti-angiogenic protein (DAAP), which can simultaneously bind VEGF-A and angiopoietins, blocking their actions. Compared to VEGF-Trap or Tie2-Fc, which block either VEGF-A or angiopoietins alone, we believe DAAP is a highly effective molecule for regressing tumor angiogenesis and metastasis in implanted and spontaneous solid tumors; it can also effectively reduce ascites formation and vascular leakage in an ovarian carcinoma model. Thus, simultaneous blockade of VEGF-A and angiopoietins with DAAP is an effective therapeutic strategy for blocking tumor angiogenesis, metastasis, and vascular leakage.
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TOP52010년 선정
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