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Updated: Dec 3, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Androgen Signaling in the Tumor Microenvironment

Berna C Özdemir1,2

  • 1Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland. berna.ozdemir@chuv.ch.

Advances in Experimental Medicine and Biology
|October 30, 2020
PubMed

Insights

Stromal androgen receptor (AR) signaling impacts prostate development and cancer. Targeting stromal AR may offer new therapeutic strategies beyond current androgen deprivation therapies.

Area of Science:

  • Endocrinology
  • Cancer Biology
  • Cellular Signaling

Background:

  • Mesenchymal/stromal androgen receptor (AR) signaling is crucial for prostate development.
  • The role of stromal AR in prostate cancer and other tissues remains incompletely understood.
  • Androgen responses differ between epithelial and stromal cells.

Purpose of the Study:

  • To investigate the function and mechanisms of stromal AR signaling.
  • To explore the dual role of stromal AR in tumor promotion and protection.
  • To assess the implications of stromal AR signaling for cancer therapies.

Main Methods:

  • Genomic analysis to compare cellular responses to androgens.
  • Investigation of AR transcription factor complexes in stromal cells.
  • Analysis of stromal AR loss in premalignant lesions and cancer progression.

Main Results:

  • Stromal AR signaling may not involve classical transcription factors like FOXA1 but utilizes the JUN/AP1 complex.
  • Stromal AR exhibits context-dependent tumor-promoting and tumor-protective functions.
  • Loss of stromal AR signaling is linked to premalignancy, tumor induction, aggressive disease, and poor prognosis in prostate cancer.
  • AR is expressed on immune cells, influencing their function.

Conclusions:

  • Stromal AR plays a significant role in various tissues beyond the prostate.
  • Current androgen deprivation therapies may have unintended consequences by inhibiting stromal AR.
  • Development of tissue-specific AR inhibitors is warranted to target stromal AR effectively.
Keywords:
ARAndrogenAndrogen receptorCAFsCancer-associated fibroblastsDendritic cellsEndothelial cellsImmunityMDSCMacrophagesProstate cancerProstate developmentStromaStromal ARTumor microenvironment

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