title: CCL2 promotes integrin-mediated adhesion of prostate cancer cells in vitro.
abstract: OBJECTIVE
  Chemokines undergo alterations during neoplasia. However, knowledge about their functional significance in prostate cancer (PCa) progression is still sparse. Since chemokine (C-C motif) ligand 2 (CCL2) is significantly up-regulated in patients with PCa, aim of the current study was to assess whether CCL2 contributes to invasive behavior of prostate cancer cells in vitro.
  
  
  METHODS
  The human PCa cell line PC3 was stimulated with CCL2. Cell growth was investigated by MTT dye reduction assay. Cell adhesion was analyzed by measuring attachment to a human endothelial cell (HUVEC) monolayer and immobilized collagen. Cell migration was assessed by a chemotactic assay. Integrin expression on the cell surface was evaluated by Western blot. Blocking studies were performed with anti-integrin α3, anti-integrin α6 and anti-integrin β4 monoclonal antibodies.
  
  
  RESULTS
  PC3 cell growth 72 h after CCL2 exposure was significantly increased, compared to controls. Activation of tumor cells by CCL2 significantly enhanced tumor cell adhesion to HUVEC and immobilized collagen. CCL2, added for 4 or 24 h, elevated α6 and β4 (4 > 24 h) integrin expression. α3 was enhanced after 4 h, but reduced after 24 h. Blocking either α3, α6 or β4 led to significant suppression of tumor cell binding to immobilized collagen.
  
  
  CONCLUSIONS
  CCL2 stimulates PCa cell adhesion and induces alterations in α3-, α6- and β4-integrin expression on the cell surface. Blocking these integrins leads to a significant reduction in cell adhesion.
authors.affiliation: Department of Urology and Pediatric Urology, Goethe-University, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany, igor.tsaur@kgu.de.
authors.forename: Igor
authors.initials: I
authors.lastname: Tsaur
authors.forename: Jochen
authors.initials: J
authors.lastname: Rutz
authors.forename: Jasmina
authors.initials: J
authors.lastname: Makarević
authors.forename: Eva
authors.initials: E
authors.lastname: Juengel
authors.forename: Kilian M
authors.initials: KM
authors.lastname: Gust
authors.forename: Hendrik
authors.initials: H
authors.lastname: Borgmann
authors.forename: David
authors.initials: D
authors.lastname: Schilling
authors.forename: Karen
authors.initials: K
authors.lastname: Nelson
authors.forename: Axel
authors.initials: A
authors.lastname: Haferkamp
authors.forename: Georg
authors.initials: G
authors.lastname: Bartsch
authors.forename: Roman A
authors.initials: RA
authors.lastname: Blaheta
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000494:pharmacology*; D006801:Humans; D016023:Integrins / Q000502:physiology; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*
chemical_list: D018932:Chemokine CCL2; D016023:Integrins