title: Heparin-binding epidermal growth factor-like growth factor is an autocrine mediator of human prostate stromal cell growth in vitro.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Primary cultures of desmin and alpha-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, [Glu52]-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.
authors: Urologic Laboratory, Children's Hospital, Division of Urologic Surgery, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors: J L
authors: JL
authors: Duque
authors: R M
authors: RM
authors: Adam
authors: J S
authors: JS
authors: Mullen
authors: J
authors: J
authors: Lin
authors: J P
authors: JP
authors: Richie
authors: M R
authors: MR
authors: Freeman
mesh_terms: D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division; D004815:Epidermal Growth Factor / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006493:Heparin; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D011467:Prostate / Q000166:cytology*; D011470:Prostatic Hyperplasia / Q000209:etiology; D051381:Rats; D017154:Stromal Cells / Q000166:cytology*
chemical_list: C587883:HBEGF protein, human; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D006493:Heparin