Discovery and mechanisms of host defense to oncogenesis: targeting the beta-defensin-1 peptide as a natural tumor inhibitor

• Type of Material: Article
• Authors: Carrie Q. Sun, Emory University; Rebecca Arnold, Emory University; Chia-Ling Hsieh, Emory University; Julia R. Dorin, University of Edinburgh; Fei Lian, Emory University; Zhenghong Li, Emory University; John A Petros, Emory University
• Language: English
• Date: 2019-03-21
• Publisher: Taylor & Francis: STM, Behavioural Science and Public Health Titles
• Publication Version: Final Published Version
• Copyright Statement: © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1080/15384047.2018.1564564
• Title of Journal or Parent Work: Cancer Biology and Therapy
• ISSN: 1538-4047
• Volume: 20
• Issue: 6
• Start Page: 774
• End Page: 786
• Grant/Funding Information: This work was supported by the Emory University Urology Department and the Medical Research Council, UK.; This study was supported by JRD funded by Medical Research Council UK.
• Keywords: Oncology; Host defense; EXPRESSION; VIRUS; MYELOID CELLS; DENDRITIC CELLS; tumor inhibitors; tumor-associated macrophages (TAMs); HER2; human defensins; SUPPRESSOR-CELLS; MACROPHAGES; POTENTIAL ROLE; MODULATION; bladder cancer; Life Sciences & Biomedicine; BETA; ANTIMICROBIAL PEPTIDE; Science & Technology; tumor therapeutics; gene expression
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery

Abstract

Human beta-defensin-1 (hBD-1) is one of a number of small cationic host-defense peptides. Besides its well-known broad-spectrum antimicrobial function, hBD-1 has recently been identified as a chromosome 8p tumor-suppressor gene. The role of hBD-1 in modulating the host immune response to oncogenesis, associated with cell signaling and potential therapeutic applications, has become increasingly appreciated over time. In this study, multiple approaches were used to illustrate hBD-1 anti-tumor activities. Results demonstrate that hBD-1 peptide alters human epidermal growth factor receptor 2 (HER2) signal transduction and represses retroviral-mediated transgene expression in cancer cells. Loss of orthologous murine defense-1 (mBD1) in mice enhances nickel sulfate-induced leiomyosarcoma and causes mouse kidney cells to exhibit increased susceptibility to HPV-16 E6/7-induced neoplastic transformation. Furthermore, for the first time, a novel function of the urine-derived hBD-1 peptide was discovered to suppress bladder cancer growth and this may lead to future applications in the treatment of malignancy.