title: Prostate stromal cells express the progesterone receptor to control cancer cell mobility.
abstract: BACKGROUND
  Reciprocal interactions between epithelium and stroma play vital roles for prostate cancer development and progression. Enhanced secretions of cytokines and growth factors by cancer associated fibroblasts in prostate tumors create a favorable microenvironment for cancer cells to grow and metastasize. Our previous work showed that the progesterone receptor (PR) was expressed specifically in prostate stromal fibroblasts and smooth muscle cells. However, the expression levels of PR and its impact to tumor microenvironment in prostate tumors are poorly understood.
  
  
  METHODS
  Immunohistochemistry assays are applied to human prostate tissue biopsies. Cell migration, invasion and proliferation assays are performed using human prostate cells. Real-time PCR and ELISA are applied to measure gene expression at molecular levels.
  
  
  RESULTS
  Immunohistochemistry assays showed that PR protein levels were decreased in cancer associated stroma when compared with paired normal prostate stroma. Using in vitro prostate stromal cell models, we showed that conditioned media collected from PR positive stromal cells inhibited prostate cancer cell migration and invasion, but had minor suppressive impacts on cancer cell proliferation. PR suppressed the secretion of stromal derived factor-1 (SDF-1) and interlukin-6 (IL-6) by stromal cells independent to PR ligands. Blocking PR expression by siRNA or supplementation of exogenous SDF-1 or IL-6 to conditioned media from PR positive stromal cells counteracted the inhibitory effects of PR to cancer cell migration and invasion.
  
  
  CONCLUSIONS
  Decreased expression of the PR in cancer associated stroma may contribute to the elevated SDF-1 and IL-6 levels in prostate tumors and enhance prostate tumor progression.
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jennifer Suehyun
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ning
authors.initials: N
authors.lastname: Xie
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Estelle
authors.initials: E
authors.lastname: Li
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Antonio
authors.initials: A
authors.lastname: Hurtado-Coll
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Cox
authors.affiliation: Department of Medicine, University of Washington School of Medicine and VAPSHCS-GRECC, Seattle, Washington, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Plymate
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Gleave
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada; Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Xuesen
authors.initials: X
authors.lastname: Dong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011980:Receptors, Progesterone / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D015850:Interleukin-6; D011980:Receptors, Progesterone