Molecular mechanism for roles of chondroitin sulfate in tumor metastasis

硫酸软骨素在肿瘤转移中作用的分子机制

• 批准号: 23390016
• 负责人: SUGAHARA Kazuyuki
• 金额: $ 11.81万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390016/
• 关键词: 癌; 転移; コンドロイチン硫酸; ヘパラン硫酸; RAGE; ルイス肺癌細胞; グリコサミノグリカン; プロテオミクス; プロテオグリカン; オリゴ糖; デルマタン硫酸

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.

此前，我们已经证明具有高转移潜能的Lewis肺癌(LLC)来源的肿瘤细胞系在CS链上显示出更高比例的E-二糖单位GlcUA-GalNAc(4，6-O-二硫酸盐)，这是由噬菌体展示抗体识别的。有趣的是，该抗体对肺转移有强烈的抑制作用。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(RAGE)。此外，抗RAGE抗体能有效地抑制LLC细胞在肺的定植。这些结果为RAGE至少是CS链在肿瘤细胞表面表达并参与实验性肺转移的关键受体之一提供了明确的证据，CS/HS和RAGE是治疗肺转移的潜在分子靶点。

项目成果

「Bone and Skin Disorders Caused by a Disturbance in the Bioynthesis of Chondroitin Sulfate and Dermatan Sulfate 」, Extracellular matrix : Pathobiology and signaling , (N. Karamanos ed.)

“硫酸软骨素和硫酸皮肤素生物合成紊乱引起的骨和皮肤疾病”，细胞外基质：病理生物学和信号传导，（N. Karamanos 编辑）

• 发表时间: 2012
• 作者: Shuji Mizumoto;Kazuyuki Sugahara
• 通讯作者: Kazuyuki Sugahara

Wobble chondroitin sulfate oligosaccharide motifs and mass production of oligosaccharides

摆动硫酸软骨素寡糖基序和寡糖的大规模生产

• 作者: Kazuyuki SUGAHARA;Jun TAKAHASHI;Shuji MIZUMOTO;Kazuyuki Sugahara
• 通讯作者: Kazuyuki Sugahara

Dermatan sulfate epimerase 2 is the predominant isozyme in the formation of the chondroitin sulfate/dermatan sulfate hybrid structure in postnatal developing mouse brain

• DOI: 10.1093/glycob/cwq208
• 发表时间: 2011-05-01
• 期刊: GLYCOBIOLOGY
• 影响因子: 4.3
• 作者: Akatsu, Chizuru;Mizumoto, Shuji;Sugahara, Kazuyuki
• 通讯作者: Sugahara, Kazuyuki

RAGEは癌細胞の肺転移に関わるコンドロイ チン硫酸の受容体として機能する

RAGE 作为硫酸软骨素受体发挥作用，硫酸软骨素参与癌细胞的肺转移。

• 发表时间: 2012
• 作者: 水本秀二,高橋潤;菅原一幸
• 通讯作者: 菅原一幸

研究業績

研究成果