Insulin-like growth factor-binding protein-5 (IGFBP-5) acts as a tumor suppressor by inhibiting angiogenesis.
Insulin-like growth factor-binding protein-5 (IGFBP-5) is one of the six members 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 antiangiostatic 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 phosphorylated protein kinase B and phosphorylated endothelial NO synthase, which plays important roles in the regulation of angiogenesis when stimulated by vascular endothelial growth factor. 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.
Rho
Seung Bae
SB
Research Institute, National Cancer Center, 809 Madu 1-dong, Ilsan-gu, Republic of Korea. sbrho@ncc.re.kr
Dong
Seung Myung
SM
Kang
Sokbom
S
Seo
Sang-Soo
SS
Yoo
Chong Woo
CW
Lee
Dong Ock
DO
Woo
Jong Soo
JS
Park
Sang-Yoon
SY
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D017931:DNA Primers; D018975:Insulin-Like Growth Factor Binding Protein 5; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III