Affordable Access

Publisher Website

HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH FACTOR IS AN AUTOCRINE MEDIATOR OF HUMAN PROSTATE STROMAL CELL GROWTH IN VITRO

Authors
Journal
The Journal of Urology
0022-5347
Publisher
Elsevier
Publication Date
Volume
165
Issue
1
Identifiers
DOI: 10.1097/00005392-200101000-00080
Keywords
  • Receptor
  • Epidermal Growth Factor
  • Prostatic Hyperplasia
  • Stroma Cells
Disciplines
  • Biology

Abstract

Purpose The physiological mechanisms by which soluble mediators of cell proliferation and survival alter expansion of the prostatic stroma in benign prostatic hyperplasia are poorly understood. We recently identified heparin-binding epidermal growth factor like growth factor (HB-EGF) as a product predominantly of the smooth muscle cell compartments of the adult human prostate. We assess the potential role of this growth factor as a stromal cell regulator. Materials and Methods Primary cultures of desmin and α-actin positive human prostate stromal cells were shown to express several cell associated HB-EGF isoforms as well as the primary cognate HB-EGF receptor, ErbB1/HER1, suggesting the existence of an autocrine or juxtacrine regulatory loop. The related receptor tyrosine kinase, ErbB2/HER2, was also expressed as assessed by reverse transcriptase (RT) polymerase chain reaction (PCR). HB-EGF messenger RNA levels in human prostate stromal cells increased modestly (70%) in response to a repetitive mechanical stimulus, a lower response than has been reported for neonatal rat bladder smooth muscle cells, in which HB-EGF was originally identified as a mechanically responsive gene. Results HB-EGF, epidermal growth factor and basic fibroblast growth factor stimulated human prostate stromal cell growth, while a specific antagonist of HB-EGF, [Glu 52]-diphtheria toxin/CRM197, inhibited human prostate stromal growth in serum-free medium by a mechanism that did not involve increased apoptosis. A function blocking antibody against CD9/DRAP27/MRP-1, a cell surface binding partner of the membrane form of HB-EGF, also stimulated human prostate stromal cell proliferation. Conclusions HB-EGF is an endogenously produced human prostate stromal cell growth factor and, thus, may have a role as a physiologically relevant autocrine or juxtacrine mediator of stromal expansion in benign prostatic hyperplasia.

There are no comments yet on this publication. Be the first to share your thoughts.