title: Critical and opposing roles of the chemokine receptors CXCR2 and CXCR3 in prostate tumor growth.
abstract: BACKGROUND
  Angiogenic and angiostatic CXC chemokines mediate their effects via the receptors, CXCR2 and CXCR3, respectively. The current study sought to determine whether the presence of these receptors alters prostate tumor growth.
  
  
  METHODS
  Endothelial cell chemotaxis of prostate cell-derived products was determined in vitro. Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice was bred with CXCR2- or CXCR3-knockout mice to determine the effects of these genes on prostate tumor growth.
  
  
  RESULTS
  Normal prostate epithelial cells release CXCR3 ligands that limit endothelial cell chemotaxis. Prostate cancer cells release CXCR2 ligands that stimulated endothelial cell chemotaxis. Tumors in TRAMP/CXCR2(-/-) mice were significantly smaller than those in TRAMP/CXCR2(+/+) mice and had reduced angiogenesis. In contrast, tumors in TRAMP/CXCR3(-/-) mice were palpable much earlier than TRAMP/CXCR3(+/+) mice and had greatly increased angiogenesis.
  
  
  CONCLUSIONS
  The data suggest that signaling through CXCR2 and CXCR3 represents important counter-regulatory mechanisms that control the growth of prostate tumors.
authors.affiliation: Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0558, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Rebecca
authors.initials: R
authors.lastname: Schuster
authors.forename: Bao
authors.initials: B
authors.lastname: Lu
authors.forename: Susan E
authors.initials: SE
authors.lastname: Waltz
authors.forename: Alex B
authors.initials: AB
authors.lastname: Lentsch
mesh_terms: D000818:Animals; D048708:Cell Growth Processes; D002633:Chemotaxis; D042783:Endothelial Cells / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000473:pathology*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000502:physiology*; D023063:Receptors, Interleukin-8B / Q000502:physiology*
chemical_list: C515187:CXCR3 protein, human; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D023063:Receptors, Interleukin-8B