Molecular mechanism for roles of chondroitin sulfate in tumor metastasis

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Previously, we have demonstrated that Lewis lung carcinoma (LLC)-derived tumor cell line with high metastatic potential shows a higher proportion of E-disaccharide units, GlcUA-GalNAc(4, 6-O-disulfate), in CS chains, which are recognized by phage display antibody. Interestingly, the antibody strongly inhibited the pulmonary metastasis. In this research, to elucidate the molecular mechanism for tumor metastasis involved in the CS chains. The receptor molecule for CS chains containing E-disaccharides, Receptor for Advanced Glycation End-products (RAGE), was identified by proteomics approach. Furthermore, the colonization of the lungs by LLC cells was effectively inhibited by an anti-RAGE antibody. These results provide the clear evidence that RAGE is at least one of the critical receptors for CS chains expressed at the tumor cell surface and involved in experimental lung metastasis, and that CS/HS and RAGE are potential molecular targets in the treatment of pulmonary metastasis.