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Sci Rep. 2016 Dec 23;6:39334. doi: 10.1038/srep39334.

The C-terminus of IGFBP-5 suppresses tumor growth by inhibiting angiogenesis.

Author information

1
Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
2
Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
3
Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.
4
Department of Immunology, School of Medicine, Konkuk University, Chungju 27478, Korea.
5
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul 02792, Korea.
6
Cancer Center, Cha Bundang Hospital, Seongnam-si, Gyeonggi-do 13496, Korea.
7
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.

Abstract

Insulin-like growth factor-binding protein 5 (IGFBP-5) plays a role in cell growth, differentiation, and apoptosis. In this study, we found that IGFBP5 was markedly downregulated in ovarian cancer tissue. We investigated the functional significance of IGFBP-5 as a tumor suppressor. To determine functional regions of IGFBP-5, truncation mutants were prepared and were studied the effect on tumor growth. Expression of C-terminal region of IGFBP-5 significantly decreased tumor growth in an ovarian cancer xenograft. A peptide derived from the C-terminus of IGFBP-5 (BP5-C) was synthesized to evaluate the minimal amino acid motif that retained anti-tumorigenic activity and its effect on angiogenesis was studied. BP5-C peptide decreased the expression of VEGF-A and MMP-9, phosphorylation of Akt and ERK, and NF-kB activity, and inhibited angiogenesis in in vitro and ex vivo systems. Furthermore, BP5-C peptide significantly decreased tumor weight and angiogenesis in both ovarian cancer orthotopic xenograft and patient-derived xenograft mice. These results suggest that the C-terminus of IGFBP-5 exerts anti-cancer activity by inhibiting angiogenesis via regulation of the Akt/ERK and NF-kB-VEGF/MMP-9 signaling pathway, and might be considered as a novel angiogenesis inhibitor for the treatment of ovarian cancer.

PMID:
28008951
PMCID:
PMC5180245
DOI:
10.1038/srep39334
[Indexed for MEDLINE]
Free PMC Article

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