[Prostatic luminal progenitors: From tissue regeneration to therapeutic escape]
Related Experiment Video
Updated: Jul 29, 2025
Evaluating the Differentiation Capacity of Mouse Prostate Epithelial Cells Using Organoid Culture
Published on: November 22, 2019
Charles Dariane1, Manon Baures2, Julien Anract3
1Université Paris Cité, Inserm UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades (INEM), Paris, France - Service d'urologie, hôpital européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
Abstract:
Inhibition of androgen signaling is the gold standard treatment of benign prostate hyperplasia and prostate cancer. Despite the initial response to these treatments, therapeutic resistance is ultimately observed in most patients. Single cell RNAseq studies have shown that castration-tolerant luminal cells share several molecular and functional features with cells identified as luminal progenitor in physiological conditions. The increased prevalence of luminal progenitor-like cells in tumor contexts might result from their intrinsic androgen-independence and from the reprogramming of differentiated luminal cells into a castration-tolerant state. Thus, it is currently hypothesized that the luminal progenitor molecular profile might constitute a functional hub for cell survival in androgen deprivation context, a prerequisite for tumor regrowth. Therapeutic intervention interfering with luminal lineage plasticity is a promising approach to prevent prostate cancer progression.
Insights
Therapeutic resistance to androgen signaling inhibition is common in prostate cancer. Luminal progenitor cells may drive tumor regrowth by surviving androgen deprivation, suggesting new treatment targets.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Context:
- Androgen signaling inhibition is standard for prostate cancer and benign prostate hyperplasia, but resistance develops.
- Castration-tolerant cells resemble luminal progenitor cells, suggesting a role in resistance.
- Prostate tumor cells can become androgen-independent, contributing to treatment failure.
Purpose:
- To investigate the role of luminal progenitor cells in therapeutic resistance to androgen deprivation.
- To explore the potential of targeting luminal lineage plasticity for prostate cancer treatment.
Summary:
- Single-cell RNA sequencing reveals castration-tolerant luminal cells share features with luminal progenitors.
- Androgen-independent luminal progenitor-like cells may promote survival and regrowth under androgen deprivation.
- Reprogramming of differentiated cells into a castration-tolerant state contributes to resistance.
Impact:
- Identifies luminal progenitor molecular profile as a potential survival hub in androgen deprivation.
- Suggests targeting luminal lineage plasticity as a novel therapeutic strategy to prevent prostate cancer progression.
- Offers insights into mechanisms of therapeutic resistance for improved treatment outcomes.
