title: Estrogen receptor α in cancer associated fibroblasts suppresses prostate cancer invasion via reducing CCL5, IL6 and macrophage infiltration in the tumor microenvironment.
abstract: BACKGROUND
  Cancer associated fibroblasts (CAF) play important roles in tumor growth that involves inflammation and epithelial cell differentiation. Early studies suggested that estrogen receptor alpha (ERα) was expressed in stromal cells in normal prostates and prostate cancer (PCa), but the detailed functions of stromal ERα in the PCa remain to be further elucidated.
  
  
  METHODS
  Migration and invasion assays demonstrated the presence of high levels of ERα in CAF cells (CAF.ERα(+)) suppressed PCa invasion via influencing the infiltration of tumor associated macrophages. ERα decreased CAF CCL5 secretion via suppressing the CCL5 promoter activity was examined by luciferase assay. ERα decreased CCL5 and IL-6 expression in conditioned media that was collected from CAF cell only or CAF cell co-cultured with macrophages as measured by ELISA assay.
  
  
  RESULTS
  Both in vitro and in vivo studies demonstrated CAF.ERα(+) led to a reduced macrophage migration toward PCa via inhibiting CAF cells secreted chemokine CCL5. This CAF.ERα(+) suppressed macrophage infiltration affected the neighboring PCa cells invasion and the reduced invasiveness of PCa cells are at least partly due to reduced IL6 expression in the macrophages and CAF.
  
  
  CONCLUSIONS
  Our data suggest that CAF ERα could be applied as a prognostic marker to predict cancer progression, and targeting CCL5 and IL6 may be applied as an alternative therapeutic approach to reduce M2 type macrophages and PCa invasion in PCa patients with low or little ERα expression in CAF cells.
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, NY, 14642, USA.
authors.forename: Chiuan-Ren
authors.initials: CR
authors.lastname: Yeh
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, NY, 14642, USA.
authors.forename: Spencer
authors.initials: S
authors.lastname: Slavin
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, NY, 14642, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Da
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, NY, 14642, USA.
authors.forename: Iawen
authors.initials: I
authors.lastname: Hsu
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, NY, 14642, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, NY, 14642, USA.
authors.forename: Guang-Qian
authors.initials: GQ
authors.lastname: Xiao
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, NY, 14642, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, NY, 14642, USA.
authors.forename: Fu-Ju
authors.initials: FJ
authors.lastname: Chou
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, NY, 14642, USA. shuyuan_yeh@urmc.rochester.edu.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D018946:Chemokine CCL5 / Q000378:metabolism*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008819:Mice, Nude; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; D017077:Culture Media, Conditioned; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D015850:Interleukin-6