title: Effects of epidermal growth factor/hydrocortisone on the growth and differentiation of human ovarian surface epithelium.
abstract: OBJECTIVE
  Ovarian surface epithelium (OSE), the precursor of the epithelial ovarian carcinomas, has limited growth potential in culture. Epidermal growth factor+hydrocortisone (EGF+HC) enhances its growth but induces epitheliomesenchymal transition (EMT). This study was undertaken to define the effects of EGF+HC and their reversibility, to optimize growth-promoting media, and to relate OSE phenotypes in vitro to physiologic states in vivo.
  
  
  METHODS
  OSE was cultured in media 199/MDCB105 or EBM (Clonetics) with 2% or 10% fetal bovine serum with or without 10 ng/mL EGF, 1.0 microg/mL HC, and 1.0 microg/mL bovine brain extract. Growth rates and growth potentials (population doublings [PD] to senescence) were defined, and growth patterns and expression of keratin and collagen types III and IV were compared with the ovarian cancer cell lines OVCAR3 and SKOV3.
  
  
  RESULTS
  EGF+HC increased growth potentials from 12-14 PD to 40-42 PD and reduced PD time from 53 hours to 20 hours. Without EGF+HC, OSE cells remained uniformly epithelial. EGF+HC induced EMT (mesenchymal shapes, reduced keratin, and production of collagenous extracellular matrix), but the EMT response varied greatly among OSE from different women. EMT was reversed over 1-2 weeks by subculture into EGF+HC-free medium in passage 1, but inconsistently thereafter. EGF+HC had no effect on the differentiation of ovarian carcinoma lines.
  
  
  CONCLUSIONS
  The phenotype of intact OSE in vivo is most closely reproduced in media without EGF+HC. EGF+HC enhances growth but initiates EMT, which likely mimics a repair response. Variations in EGF+HC-induced phenotypes point to the existence of OSE subpopulations with differing responsiveness to growth factors or steroids, which may relate to their susceptibility to malignant transformation.
authors.affiliation: Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Clara M
authors.initials: CM
authors.lastname: Salamanca
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Maines-Bandiera
authors.forename: Peter C K
authors.initials: PC
authors.lastname: Leung
authors.forename: Yu-Long
authors.initials: YL
authors.lastname: Hu
authors.forename: Nelly
authors.initials: N
authors.lastname: Auersperg
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D024061:Collagen Type III / Q000096:biosynthesis / Q000235:genetics; D024141:Collagen Type IV / Q000096:biosynthesis / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007633:Keratins / Q000096:biosynthesis / Q000235:genetics; D008856:Microscopy, Fluorescence; D010053:Ovary / Q000166:cytology*; D010641:Phenotype; D014407:Tumor Cells, Cultured
chemical_list: D024061:Collagen Type III; D024141:Collagen Type IV; D004815:Epidermal Growth Factor; D007633:Keratins; D006854:Hydrocortisone