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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.

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


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.

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