Differential gene expression profiling of functionally and developmentally distinct human prostate epithelial...

Area of Science:

• Urology
• Developmental Biology
• Cancer Research

Background:

• Human prostate development involves androgen-driven branching morphogenesis starting at the 10th gestational week.
• Adult basal epithelial cells expressing Epcam⁺ CD44⁻ CD49f(Hi) demonstrate efficient tubule formation.
• Fetal prostate development and adult tubule-initiating cells (TIC) share similarities in stromal interactions and branching morphogenesis.

Purpose of the Study:

• To evaluate in vivo tubule initiation by human fetal prostate cells.
• To determine and compare gene expression profiles of fetal and adult prostate epithelial subpopulations.
• To identify pathways utilized by tubule-initiating cells (TIC).

Main Methods:

• Immunostaining and fluorescence-activated cell sorting (FACS) were used to characterize fetal prostate epithelial cells (FC) based on Epcam, CD44, and CD49f expression.
• Isolated fetal cells were implanted into immunocompromised mice to assess in vivo tubule formation.
• Microarray analysis was performed on sorted fetal and adult prostate epithelial cells (FC, TIC, basal cells (BC), luminal cells (LC)) to compare gene expression profiles.

Main Results:

• Fetal prostate epithelial cell implants formed tubules and differentiated into basal and luminal compartments.
• Hierarchical clustering identified distinct gene expression profiles for fetal cells (FC), tubule-initiating cells (TIC), basal cells (BC), and luminal cells (LC).
• Fetal cells exhibited gene expression profiles most similar to adult TIC, with many shared pathways implicated in prostate tumorigenesis.

Conclusions:

• Gene expression profiles of fetal prostate cells (FC) closely resemble those of adult tubule-initiating cells (TIC).
• Pathways associated with TIC are frequently deregulated in prostate cancer.
• These findings suggest that TIC may play a cell-of-origin role in prostate tumorigenesis.