Peroxiredoxin 1 Controls Prostate Cancer Growth through Toll-Like Receptor 4―Dependent Regulation of Tumor Vasculature

In recent years a number of studies have implicated chronic inflammation in prostate carcinogenesis. However, mitigating factors of inflammation in the prostate are virtually unknown. Toll-like receptor 4 (TLR4) activity is associated with inflammation and is correlated with progression risk in pros...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2011-03, Vol.71 (5), p.1637-1646
Main Authors: RIDDELL, Jonah R, BSHARA, Wiam, MOSER, Michael T, SPERNYAK, Joseph A, FOSTER, Barbara A, GOLLNICK, Sandra O
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Cell Differentiation
Cell Movement
Cell Proliferation
Endothelial Cells - cytology
Endothelial Cells - metabolism
Gynecology. Andrology. Obstetrics
Humans
Immunohistochemistry
Male
Male genital diseases
Medical sciences
Mice
Mice, Inbred C57BL
Mice, SCID
Neovascularization, Pathologic - metabolism
Nephrology. Urinary tract diseases
Peroxiredoxins - metabolism
Pharmacology. Drug treatments
Prostatic Neoplasms - blood supply
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Tissue Array Analysis
Toll-Like Receptor 4 - metabolism
Tumors
Tumors of the urinary system
Urinary tract. Prostate gland
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In recent years a number of studies have implicated chronic inflammation in prostate carcinogenesis. However, mitigating factors of inflammation in the prostate are virtually unknown. Toll-like receptor 4 (TLR4) activity is associated with inflammation and is correlated with progression risk in prostate cancer (CaP). TLR4 ligands include bacterial cell wall proteins, danger signaling proteins, and intracellular proteins such as heat shock proteins and peroxiredoxin 1 (Prx1). Here we show that Prx1 is overexpressed in human CaP specimens and that it regulates prostate tumor growth through TLR4-dependent regulation of prostate tumor vasculature. Inhibiting Prx1 expression in prostate tumor cells reduced tumor vascular formation and function. Furthermore, Prx1 inhibition reduced levels of angiogenic proteins such as VEGF within the tumor microenvironment. Lastly, Prx1-stimulated endothelial cell proliferation, migration, and differentiation in a TLR4- and VEGF-dependent manner. Taken together, these results implicate Prx1 as a tumor-derived inducer of inflammation, providing a mechanistic link between inflammation and TLR4 in prostate carcinogenesis. Our findings implicate Prx1 as a novel therapeutic target for CaP.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-10-3674