Receptor for Advanced Glycation End Products Functions as a Receptor for Glycosaminoglycans in Lung Metastasis

Abstract

Glycosaminoglycans (GAGs) at cell surfaces of cancer cells play roles in malignant transformation and metastasis. Highly metastatic Lewis lung carcinoma cells showed a strong expression of the chondroitin sulfate E (CS‐E) epitope consisting of the E‐disaccharide unit GlcUA‐GalNAc(4, 6‐O‐disulfate). The metastasis was efficiently inhibited in a mouse system by enzymatic removal of CS from the tumor cell surface or by pre‐injection of CS‐E in a dose‐dependent manner (Li et al., J. Biol. Chem. 2008). These findings prompted us to investigate the roleof the CS and/or GAG structure of the tumor cells in the experimental lung metastasis.In this study to characterize CS‐E‐binding proteins in a mouse lung, an extract of a mouse lung homogenate was analyzed by affinity chromatography using a CS‐E‐immobilized column. A CS‐E‐binding putative receptor was identified as Receptor for Advanced Glycation End products (RAGE) by SDS‐PAGE followed by MALDI‐TOF‐MS of the trypsin digest of a protein band, suggesting that the E‐unit‐containing epitopes of CS chains as well as heparan sulfate chains at the tumor cell surfaces are recognized by RAGE in the lung, and are promising targets for diagnosis and therapy of malignant tumors (S. Mizumoto, J. Takahashi, and K. Sugahara, submitted).This work was supported by a Grant‐in‐aid for Scientific Research (B) and Future Drug Discovery and Medical Care Innovation Program from MEXT (to KS).