Login to Access Video or Poster Abstract: MP17-10
Sources of Funding: 1U54 DK112079 and 1R56 DK107492

Introduction

Prostate specific antigen (PSA), which is expressed by luminal epithelial cells in prostate was recently shown in the stromal compartment of BPH. Since the stromal compartment does not express PSA, epithelial barrier integrity in BPH nodules might be compromised through loss of cell junctions, resulting in the leakage of PSA and other secreted proteins into the stromal compartment and subsequently promoting BPH pathogenesis. E-cadherin, an important cell junction regulator, is found to be down-regulated in epithelial cells in clinical BPH specimens. Whether E-cadherin downregulation affects epithelial barrier permeability is unknown. This research is aimed at examining epithelial barrier permeability change in BPH and exploring the potential role of E-cadherin in prostatic luminal epithelial permeability.

Methods

Explants derived from BPH patients were used to study epithelial barrier permeability in BPH nodules and its normal adjacent tissues by FITC-dextran assay. Normal prostate luminal epithelial cell line BHPrE1 was utilized to perform in vitro studies. Two independent siRNAs were used to knockdown E-cadherin expression. Permeability of BHPrE1 cell monolayers in trans-well inserts was evaluated by trans-epithelium electrical resistant (TER) assay and FITC-dextran trans-well assay. Cell viability was checked by cell counting assay and MTT assay. Expression of E-cadherin and tight junction proteins following siRNAs treatment were determined by reverse transcription-polymerase chain reaction (RT-PCR) and western-blot (WB).

Results

FITC-dextran assay detected an increased epithelial barrier permeability in BPH tissues but not in the adjacent normal prostate in explants derived from BPH patients. Knockdown of E-cadherin in BHPrE1 cells decreased TER and increased FITC-dextran diffusion, indicating that E-cadherin knockdown disrupted epithelial barrier and increased monolayer permeability. E-cadherin knockdown had no impact on cell viability. E-cadherin knockdown also did not affect the expression of tight junction proteins ZO-1, ZO-2 and ZO-3.

Conclusions

Epithelial barrier permeability was increased in BPH and loss of E-cadherin is potentially an important underlying mechanism. Our results suggest blocking E-cadherin loss could be a potential approach to prevent or treat BPH.

Funding

1U54 DK112079 and 1R56 DK107492