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

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

Fingerprint

Defensins
Carcinogenesis
Peptides
Neoplasms
Human papillomavirus 16
Leiomyosarcoma
Tumor Suppressor Genes
Transgenes
Urinary Bladder Neoplasms
human DEFB1 protein
Signal Transduction
Chromosomes
Urine
Kidney
Growth

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

Cite this

Discovery and mechanisms of host defense to oncogenesis : targeting the β-defensin-1 peptide as a natural tumor inhibitor. / Sun, Carrie Q.; Arnold, Rebecca S.; Hsieh, Chia Ling; Dorin, Julia R.; Lian, Fei; Li, Zhenghong; Petros, John A.

In: Cancer Biology and Therapy, Vol. 20, No. 6, 03.06.2019, p. 774-786.

Research output: Contribution to journalArticle

Sun, Carrie Q. ; Arnold, Rebecca S. ; Hsieh, Chia Ling ; Dorin, Julia R. ; Lian, Fei ; Li, Zhenghong ; Petros, John A. / Discovery and mechanisms of host defense to oncogenesis : targeting the β-defensin-1 peptide as a natural tumor inhibitor. In: Cancer Biology and Therapy. 2019 ; Vol. 20, No. 6. pp. 774-786.
@article{ffbd6fd68ee5405a98261147915c2ce5,
title = "Discovery and mechanisms of host defense to oncogenesis: targeting the β-defensin-1 peptide as a natural tumor inhibitor",
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.",
keywords = "bladder cancer, gene expression, HER2, Host defense, human defensins, tumor inhibitors, tumor therapeutics, tumor-associated macrophages (TAMs)",
author = "Sun, {Carrie Q.} and Arnold, {Rebecca S.} and Hsieh, {Chia Ling} and Dorin, {Julia R.} and Fei Lian and Zhenghong Li and Petros, {John A.}",
year = "2019",
month = "6",
day = "3",
doi = "10.1080/15384047.2018.1564564",
language = "English",
volume = "20",
pages = "774--786",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "6",

}

TY - JOUR

T1 - Discovery and mechanisms of host defense to oncogenesis

T2 - targeting the β-defensin-1 peptide as a natural tumor inhibitor

AU - Sun, Carrie Q.

AU - Arnold, Rebecca S.

AU - Hsieh, Chia Ling

AU - Dorin, Julia R.

AU - Lian, Fei

AU - Li, Zhenghong

AU - Petros, John A.

PY - 2019/6/3

Y1 - 2019/6/3

N2 - 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.

AB - 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.

KW - bladder cancer

KW - gene expression

KW - HER2

KW - Host defense

KW - human defensins

KW - tumor inhibitors

KW - tumor therapeutics

KW - tumor-associated macrophages (TAMs)

UR - http://www.scopus.com/inward/record.url?scp=85063293557&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063293557&partnerID=8YFLogxK

U2 - 10.1080/15384047.2018.1564564

DO - 10.1080/15384047.2018.1564564

M3 - Article

VL - 20

SP - 774

EP - 786

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

SN - 1538-4047

IS - 6

ER -