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Carcinogenesis Advance Access published online on September 4, 2008
Carcinogenesis, doi:10.1093/carcin/bgn206
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Insulin-like growth factor binding protein-5 (IGFBP-5) acts as a tumor suppressor by inhibiting angiogenesis

Taehoon Chun2, Seung Myung Dong1, Sang-Hoon Kim2, Sokbom Kang3, Sang-Soo Seo3, Chong Woo Yoo3, Dong Ock Lee3, Sang-Yoon Park3 and Seung Bae Rho1,*

1 Research Institute, National Cancer Center, 809, Madu 1-dong, Ilsan-gu, Goyang-si, Gyeonggi-do 411-769, Republic of Korea
2 Division of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea
3 Center for Uterine Cancer, Research Institute, National Cancer Center, 809, Madu 1-dong, Ilsan-gu, Goyang-si, Gyeonggi-do 411-769, Republic of Korea

* To whom correspondence should be addressed. Tel. +82 31 920 2383; Fax: +82 31 920 2337; E-mail: sbrho{at}ncc.re.kr

Insulin-like growth factor binding protein-5 (IGFBP-5) is one of IGFBP family, important for cell growth control, induction of apoptosis, and other IGF-stimulated signaling pathways. In this study, we focused on characterizing the specific function of IGFBP-5 as novel anti-angiostatic factor. Overexpression of IGFBP-5 suppressed the tube formation as well as the biological functions of angiostatic activity in vivo. This result is due to the reduced expressions of phosphoylated Akt and phosphorylated endothelial NO synthase (eNOS), which plays important roles in the regulation of angiogenesis when stimulated by vascular endothelial growth factor (VEGF). Further, IGFBP-5 expression prevented tumor growth and inhibited tumor vascularity in a xenograft model of human ovarian cancer. These results are the first evidence showing that IGFBP-5 plays a role as tumor suppressor by inhibiting angiogenesis.

Key Words: angiogenesis • human umbilical vein endothelial cell • insulin-like growth factor binding protein-5 • therapeutic target • tumor suppressor

Received July 2, 2008; revised August 12, 2008; accepted August 23, 2008.


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