title: The C-terminus of IGFBP-5 suppresses tumor growth by inhibiting angiogenesis.
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.
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
authors.forename: Jae Ryoung
authors.initials: JR
authors.lastname: Hwang
authors.affiliation: 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.
authors.forename: Young-Jae
authors.initials: YJ
authors.lastname: Cho
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
authors.forename: Yoonna
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
authors.forename: Youngmee
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungju 27478, Korea.
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul 02792, Korea.
authors.forename: Hyung Jun
authors.initials: HJ
authors.lastname: Ahn
authors.affiliation: Cancer Center, Cha Bundang Hospital, Seongnam-si, Gyeonggi-do 13496, Korea.
authors.forename: Je-Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: 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 Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Lee
mesh_terms: D000818:Animals; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000473:pathology*; D017384:Sequence Deletion; D015398:Signal Transduction
chemical_list: D018975:Insulin-Like Growth Factor Binding Protein 5