Double antiangiogenic protein, DAAP, targeting VEGF-A and angiopoietins in tumor angiogenesis, metastasis, and vascular leakage

Young Jun Koh; Hak Zoo Kim; Seong Ik Hwang; Jeung Eun Lee; Nuri Oh; Keehoon Jung; Minah Kim; Kyung Eun Kim; Homin Kim; Nam Kyu Lim; Choon Ju Jeon; Gyun Min Lee; Byeong Hwa Jeon; Do Hyun Nam; Hoon Ki Sung; Andras Nagy; Ook Joon Yoo; Gou Young Koh

doi:10.1016/j.ccr.2010.07.001

Double antiangiogenic protein, DAAP, targeting VEGF-A and angiopoietins in tumor angiogenesis, metastasis, and vascular leakage

Young Jun Koh, Hak Zoo Kim, Seong Ik Hwang, Jeung Eun Lee, Nuri Oh, Keehoon Jung, Minah Kim, Kyung Eun Kim, Homin Kim, Nam Kyu Lim, Choon Ju Jeon, Gyun Min Lee, Byeong Hwa Jeon, Do Hyun Nam, Hoon Ki Sung, Andras Nagy, Ook Joon Yoo, Gou Young Koh

Research output: Contribution to journal › Article › peer-review

140 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	171-184
Number of pages	14
Journal	Cancer Cell
Volume	18
Issue number	2
DOIs	https://doi.org/10.1016/j.ccr.2010.07.001
State	Published - Aug 2010
Externally published	Yes

Bibliographical note

Funding Information:
We thank Jin Sun Hong and Eun Soon Lee for their technical assistance, Dr. N. Gale for Ang-2 +/LacZ mice, Dr. K.K. Kim for CT-26-luc cells, Dr. K. Roby for ID-8 cells, and Dr. Rolf Brekken for anti-VEGFR2 antibody. This work was supported by the Korea Science and Engineering Foundation (KOSEF) funded by the MEST (R2009-0079390 and R31-2009-000-10071-0 to G.Y.K.) and the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Korea (A092255 to G.Y.K.).

Keywords

Cellcycle

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccr.2010.07.001

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Koh, Y. J., Kim, H. Z., Hwang, S. I., Lee, J. E., Oh, N., Jung, K., Kim, M., Kim, K. E., Kim, H., Lim, N. K., Jeon, C. J., Lee, G. M., Jeon, B. H., Nam, D. H., Sung, H. K., Nagy, A., Yoo, O. J., & Koh, G. Y. (2010). Double antiangiogenic protein, DAAP, targeting VEGF-A and angiopoietins in tumor angiogenesis, metastasis, and vascular leakage. Cancer Cell, 18(2), 171-184. https://doi.org/10.1016/j.ccr.2010.07.001

@article{0b8b1018d3ce447f8c1d29cae3bee708,

title = "Double antiangiogenic protein, DAAP, targeting VEGF-A and angiopoietins in tumor angiogenesis, metastasis, and vascular leakage",

abstract = "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.",

keywords = "Cellcycle",

author = "Koh, \{Young Jun\} and Kim, \{Hak Zoo\} and Hwang, \{Seong Ik\} and Lee, \{Jeung Eun\} and Nuri Oh and Keehoon Jung and Minah Kim and Kim, \{Kyung Eun\} and Homin Kim and Lim, \{Nam Kyu\} and Jeon, \{Choon Ju\} and Lee, \{Gyun Min\} and Jeon, \{Byeong Hwa\} and Nam, \{Do Hyun\} and Sung, \{Hoon Ki\} and Andras Nagy and Yoo, \{Ook Joon\} and Koh, \{Gou Young\}",

note = "Funding Information: We thank Jin Sun Hong and Eun Soon Lee for their technical assistance, Dr. N. Gale for Ang-2 +/LacZ mice, Dr. K.K. Kim for CT-26-luc cells, Dr. K. Roby for ID-8 cells, and Dr. Rolf Brekken for anti-VEGFR2 antibody. This work was supported by the Korea Science and Engineering Foundation (KOSEF) funded by the MEST (R2009-0079390 and R31-2009-000-10071-0 to G.Y.K.) and the Korea Healthcare Technology R\&D Project, Ministry for Health, Welfare and Family Affairs, Korea (A092255 to G.Y.K.). ",

year = "2010",

month = aug,

doi = "10.1016/j.ccr.2010.07.001",

language = "English",

volume = "18",

pages = "171--184",

journal = "Cancer Cell",

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Koh, YJ, Kim, HZ, Hwang, SI, Lee, JE, Oh, N, Jung, K, Kim, M, Kim, KE, Kim, H, Lim, NK, Jeon, CJ, Lee, GM, Jeon, BH, Nam, DH, Sung, HK, Nagy, A, Yoo, OJ & Koh, GY 2010, 'Double antiangiogenic protein, DAAP, targeting VEGF-A and angiopoietins in tumor angiogenesis, metastasis, and vascular leakage', Cancer Cell, vol. 18, no. 2, pp. 171-184. https://doi.org/10.1016/j.ccr.2010.07.001

TY - JOUR

T1 - Double antiangiogenic protein, DAAP, targeting VEGF-A and angiopoietins in tumor angiogenesis, metastasis, and vascular leakage

AU - Koh, Young Jun

AU - Kim, Hak Zoo

AU - Hwang, Seong Ik

AU - Lee, Jeung Eun

AU - Oh, Nuri

AU - Jung, Keehoon

AU - Kim, Minah

AU - Kim, Kyung Eun

AU - Kim, Homin

AU - Lim, Nam Kyu

AU - Jeon, Choon Ju

AU - Lee, Gyun Min

AU - Jeon, Byeong Hwa

AU - Nam, Do Hyun

AU - Sung, Hoon Ki

AU - Nagy, Andras

AU - Yoo, Ook Joon

AU - Koh, Gou Young

N1 - Funding Information: We thank Jin Sun Hong and Eun Soon Lee for their technical assistance, Dr. N. Gale for Ang-2 +/LacZ mice, Dr. K.K. Kim for CT-26-luc cells, Dr. K. Roby for ID-8 cells, and Dr. Rolf Brekken for anti-VEGFR2 antibody. This work was supported by the Korea Science and Engineering Foundation (KOSEF) funded by the MEST (R2009-0079390 and R31-2009-000-10071-0 to G.Y.K.) and the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Korea (A092255 to G.Y.K.).

PY - 2010/8

Y1 - 2010/8

N2 - 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.

AB - 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.

KW - Cellcycle

UR - https://www.scopus.com/pages/publications/77955534812

U2 - 10.1016/j.ccr.2010.07.001

DO - 10.1016/j.ccr.2010.07.001

M3 - Article

C2 - 20708158

AN - SCOPUS:77955534812

SN - 1535-6108

VL - 18

SP - 171

EP - 184

JO - Cancer Cell

JF - Cancer Cell

IS - 2

ER -

Double antiangiogenic protein, DAAP, targeting VEGF-A and angiopoietins in tumor angiogenesis, metastasis, and vascular leakage

Abstract

Bibliographical note

Keywords

UN SDGs

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