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

Carrie Q. Sun, Rebecca S. Arnold, Chia Ling Hsieh, Julia R. Dorin, Fei Lian, Zhenghong Li, John A. Petros

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)774-786
Number of pages13
JournalCancer Biology and Therapy
Volume20
Issue number6
DOIs
Publication statusPublished - Jun 3 2019
Externally publishedYes

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Keywords

  • bladder cancer
  • gene expression
  • HER2
  • Host defense
  • human defensins
  • tumor inhibitors
  • tumor therapeutics
  • tumor-associated macrophages (TAMs)

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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