Molecular mechanism for roles of chondroitin sulfate in tumor metastasis

以前，我们已经证明，刘易斯肺癌（LLC）衍生的肿瘤细胞系具有高转移潜力，显示出较高比例的E-二糖单位，GlcUA-GalNAc（4，6-O-二硫酸盐），在CS链，这是识别的噬菌体展示抗体。有趣的是，抗体强烈抑制肺转移。本研究旨在阐明CS链参与肿瘤转移的分子机制。用蛋白质组学方法鉴定了含有E-二糖的CS链的受体分子--晚期糖基化终产物受体（Receptor for Advanced Glycation End-products，RECEPTOR）。此外，LLC细胞对肺的定殖被抗-抗-IL-10抗体有效地抑制。这些结果提供了明确的证据表明，CS/HS和C12是至少在肿瘤细胞表面表达的CS链的关键受体之一，并且参与实验性肺转移，并且CS/HS和C12是治疗肺转移的潜在分子靶点。

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.