English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

The tumor microenvironment plays a critical role in supporting cancer cells particularly as they disengage from limitations on their growth and motility imposed by surrounding nonreactive stromal cells. We show here that stromal-derived androgenic precursors are metabolized by DU145 human prostate cancer (PCa) cells to generate ligands for estrogen receptor-β, which act to limit their motility through transcriptional regulation of E-cadherin. Although primary human PCa-associated fibroblasts and the human WPMY-1-reactive prostate stromal cell line maintain this inherent estrogen receptor (ER)β-dependent motility inhibitor activity, they are subverted by TGF-β1 pro-oxidant signals derived from cocultured DU145 PCa cells. Specifically, stromal-produced H2O2, which requires Cox-2, acts as a second paracrine factor to inhibit ERβ activity in adjacent DU145 cells. Chromatin immunoprecipitation analysis reveals that ERβ recruitment to the E-cadherin promoter is inhibited when H2O2 is present. Both neutralization of H2O2 with catalase and prevention of its production by silencing Cox-2 expression in stromal cells restore the motility-suppression activity of stromal-derived ERβ ligand precursors. These data suggest that reactive stromal cells may still have a capacity to limit cancer cell motility through a local endocrine network but must be protected from pro-oxidant signals triggered by cancer cell-derived TGF-β1 to exhibit this cancer-suppressive function.

molecular endocrinology

A Local Paracrine and Endocrine Network Involving TGFβ, Cox-2, ROS, and Estrogen Receptor β Influences Reactive Stromal Cell Regulation of Prostate Cancer Cell Motility