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V domain of RAGE interacts with AGEs on prostate carcinoma cells
Author(s) -
Allmen Edith Uetzvon,
Koch Michael,
Fritz Günter,
Legler Daniel F.
Publication year - 2008
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20736
Subject(s) - rage (emotion) , prostate cancer , glycation , cancer research , receptor , antibody , hmgb1 , androgen receptor , chemistry , medicine , endocrinology , immunology , biology , cancer , neuroscience
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 β 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. Prostate 68: 748–758, 2008. © 2008 Wiley‐Liss, Inc.