title: Anterograde trafficking of CXCR4 and CCR2 receptors in a prostate cancer cell line.
abstract: BACKGROUND
  Most prostate cancer-related deaths result from metastasis. CXCR4 and CCR2 are known to govern cellular processes resulting in cell migration, proliferation and survival. These receptors are expressed at low levels on normal prostate cells and are highly expressed on malignant and metastatic prostate cancer cells. Signaling of these receptors is relatively well understood, but processes governing their expression at the cell membrane are not. PC3 prostate cancer cells were used to demonstrate the importance of various Rab GTPases on cell surface expression and signaling of CXCR4 and CCR2, along with the CXCR4/CCR2 heterodimer.
  
  
  METHODS
  PC3 prostate cancer cells were transfected with select Rab GTPase wild-type and dominant negative constructs. Effects of each Rab GTPase on endogenous cell surface expression of the individual receptors, along with the overexpressed CXCR4/CCR2 heterodimer, were determined by biotin-streptavidin cell surface assays. These results were corroborated by assessing signal transduction, measured by focal adhesion kinase (FAK) activation.
  
  
  CONCLUSIONS
  Rab GTPases required for cell surface expression and signal transduction of CXCR4 or CCR2 differ from those required for the CXCR4/CCR2 heterodimer. Determining trafficking regulators of two key receptors involved in the metastatic transition may identify new targets to restrict expression of chemokine receptors employed during metastasis.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
authors.forename: Kelsie
authors.initials: K
authors.lastname: Gillies
authors.forename: Jaime
authors.initials: J
authors.lastname: Wertman
authors.forename: Nicholle
authors.initials: N
authors.lastname: Charette
authors.forename: Denis J
authors.initials: DJ
authors.lastname: Dupré
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D019281:Dimerization; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D021381:Protein Transport; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D054390:Receptors, CCR2; D019718:Receptors, CXCR4; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020691:rab GTP-Binding Proteins