title: Positive correlation between PEDF expression levels and macrophage density in the human prostate.
abstract: BACKGROUND
  In this study, we investigated the capacity of pigment epithelium-derived factor (PEDF) to modulate the recruitment and the differentiation of monocytes/macrophages both in vitro and in human prostate.
  
  
  METHODS
  Using Boyden chambers, we assessed PEDF effect on the migration of monocytes and chemically activated RAW 264.7 macrophages. Normal, prostatitis, and prostate cancer specimens were retrospectively selected and examined by immunohistochemistry for PEDF expression and infiltration of immune CD68 + macrophagic cells. PEDF expression and macrophage density were then correlated with each other and clinicopathological parameters. M1 and M2 differentiation markers were quantified by qRT-PCR, Western blotting, and ELISA.
  
  
  RESULTS
  In chemotaxis, PEDF induced the migration of monocytes/macrophages. In immunohistochemistry, macrophages were markedly increased in prostatitis and malignant compared to normal tissues. PEDF was expressed at variable levels in the stroma and epithelium. PEDF mRNA was down-regulated in both prostate cancer and prostatitis compared to normal tissues. In correlation studies, macrophage density and PEDF expression were respectively positively and negatively associated with prostate size. Most importantly, PEDF expression positively correlated with macrophage density. Finally, PEDF stimulated the expression of iNOS, IL12, and TNFα; and inhibited IL10 and arginase 1 in mouse and human macrophages confirming a M1-type differentiation.
  
  
  CONCLUSIONS
  Our data demonstrate that PEDF acts directly on monocytes/macrophages by inducing their migration and differentiation into M1-type cells. These findings suggest a possible role of macrophages in PEDF anti-tumor properties and may support further development of PEDF-based anti-cancer therapy.
authors.affiliation: Department of Urology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430-6591, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nelius
authors.forename: Christina
authors.initials: C
authors.lastname: Samathanam
authors.forename: Dalia
authors.initials: D
authors.lastname: Martinez-Marin
authors.forename: Natalie
authors.initials: N
authors.lastname: Gaines
authors.forename: Jessica
authors.initials: J
authors.lastname: Stevens
authors.forename: Johnny
authors.initials: J
authors.lastname: Hickson
authors.forename: Werner
authors.initials: W
authors.lastname: de Riese
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Filleur
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology*; D008297:Male; D051379:Mice; D009000:Monocytes / Q000166:cytology; D060787:Neoplasm Grading; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D011467:Prostate / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D011472:Prostatitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005136:Eye Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C067980:CD68 antigen, human; D000097382:CD68 Molecule