Hwang, Jae Ryoung Cho, Young-Jae Lee, Yoonna Park, Youngmee Han, Hee Dong Ahn, Hyung Jun Lee, Je-Ho Lee, Jeong-Won 2024-01-20T02:33:23Z 2024-01-20T02:33:23Z 2021-09-05 2016-12-23 2045-2322 https://pubs.kist.re.kr/handle/201004/123301 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. English NATURE PUBLISHING GROUP FACTOR-BINDING PROTEIN-5 NF-KAPPA-B EPITHELIAL OVARIAN-CANCER ENDOTHELIAL-CELLS HEPARIN-BINDING FACTOR EXPRESSION PROGNOSTIC-FACTOR VEGF EXPRESSION CARCINOMA PATHWAY The C-terminus of IGFBP-5 suppresses tumor growth by inhibiting angiogenesis Article 10.1038/srep39334 1 SCIENTIFIC REPORTS, v.6 SCIENTIFIC REPORTS 6 scie scopus 000390410400001 2-s2.0-85007109374 Multidisciplinary Sciences Science & Technology - Other Topics Article FACTOR-BINDING PROTEIN-5 NF-KAPPA-B EPITHELIAL OVARIAN-CANCER ENDOTHELIAL-CELLS HEPARIN-BINDING FACTOR EXPRESSION PROGNOSTIC-FACTOR VEGF EXPRESSION CARCINOMA PATHWAY IGFBP-5 tumor suppressor ovarian cancer