V domain of RAGE interacts with AGEs on prostate carcinoma cells
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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.
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UETZ-VON ALLMEN, Edith, Michael KOCH, Günter FRITZ, Daniel F. LEGLER, 2008. V domain of RAGE interacts with AGEs on prostate carcinoma cells. In: The Prostate. 2008, 68(7), pp. 748-758. ISSN 0270-4137. eISSN 1097-0045. Available under: doi: 10.1002/pros.20736BibTex
@article{UetzvonAllmen2008domai-36618, year={2008}, doi={10.1002/pros.20736}, title={V domain of RAGE interacts with AGEs on prostate carcinoma cells}, number={7}, volume={68}, issn={0270-4137}, journal={The Prostate}, pages={748--758}, author={Uetz-von Allmen, Edith and Koch, Michael and Fritz, Günter and Legler, Daniel F.} }
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