title: V domain of RAGE interacts with AGEs on prostate carcinoma cells.
abstract: BACKGROUND
  The expression of the scavenger receptor for advanced glycation end products (RAGE) and various ligands of RAGE correlate significantly with cancer progression. However, the mechanism of RAGE/sRAGE-induced cancer cell activation and ligand usage remain largely unknown.
  
  
  METHODS
  Androgen-independent, highly invasive, as well as androgen-dependent, non-invasive human prostate carcinoma (CaP) cells were investigated for their interaction with the soluble form of RAGE (sRAGE). Using neutralizing antibodies and soluble proteins, the ligand for RAGE was identified on CaP cells and ligand binding with sRAGE was biochemically characterized.
  
  
  RESULTS
  Both androgen-independent, highly invasive and androgen-dependent, non-invasive CaP cells interacted with immobilized sRAGE in a surprisingly strong manner. Using C-terminal truncation variants of RAGE we identified the V domain being responsible for the adhesion of CaP cells to sRAGE. Moreover, we demonstrate that this adhesion cannot be blocked by S100B or neutralizing antibodies against beta integrins, or amphoterin. However, the CaP cell-RAGE interaction was inhibited with either AGE-modified proteins, or with neutralizing antibodies against AGE or RAGE. Despite similar binding kinetics between AGE-modified BSA and different RAGE domains, only applying an excess of sRAGE, but not the VC1 or V domain of RAGE, was able to block the CaP cell-RAGE interaction.
  
  
  CONCLUSIONS
  We identified AGEs as the ligand for RAGE on both invasive and non-invasive prostate cancer cells.
authors.affiliation: Biotechnology Institute Thurgau, University of Konstanz, Kreuzlingen, Switzerland.
authors.forename: Edith Uetz-von
authors.initials: EU
authors.lastname: Allmen
authors.forename: Michael
authors.initials: M
authors.lastname: Koch
authors.forename: Günter
authors.initials: G
authors.lastname: Fritz
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Legler
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000378:metabolism*; D024243:HMGB1 Protein / Q000276:immunology; D006801:Humans; D008024:Ligands; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000276:immunology / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; D008024:Ligands; D009414:Nerve Growth Factors; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human