Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting basic fibroblast growth factor, combats tumor angiogenesis and metastasis
文献类型：期刊论文
| 作者 | Zhao, Huajun; Liu, Haiying; Chen, Yi ; Xin, Xianliang; Li, Jing; Hou, Yongtai; Zhang, Zhonghua; Zhang, Xiongwen; Me, Chengying; Geng, Meiyu
|
| 刊名 | CANCER RESEARCH
 |
| 出版日期 | 2006-09-01 |
| 卷号 | 66期号:17页码:8779-8787 |
| ISSN号 | 0008-5472 |
| DOI | 10.1158/0008-5472.CAN-06-1382 |
| 文献子类 | Article |
| 英文摘要 | Inhibitors of tumor angiogenesis and metastasis are increasingly emerging as promising agents for cancer therapy. Recently, heparanase inhibitors have offered a new avenue for such work because heparanase is thought to be critically involved in the metastatic and angiogenic potentials of tumor cells. Here, we report that oligomannurarate sulfate (JG3), a novel marine-derived oligosaccharide, acts as a heparanase inhibitor. Our results revealed that JG3 significantly inhibited tumor angiogenesis and metastasis, both in vitro and in vivo, by combating heparanase activity via binding to the KKDC and QPLK domains of the heparanase molecule. The JG3-heparanase interaction was competitively inhibited by low molecular weight heparin (4,000 Da) but not by other glycosaminoglycans. in addition, JG3 abolished heparanase-driven invasion, inhibited the release of heparan sulfate-sequestered basic fibroblast growth factor (bFGF) from the extracellular matrix, and repressed subsequent angiogenesis. Moreover, JG3 inactivated bFGF-induced bFGF receptor and extracellular signal-regulated kinase 1/2 phosphorylation and blocked bFGF-triggered angiogenic events by directly binding to bFGF. Thus, JG3 seems to inhibit both major heparanase activities by simultaneously acting as a substrate mimetic and as a competitive inhibitor of heparan sulfate. These findings suggest that JG3 should be considered as a promising candidate agent for cancer therapy. |
| WOS关键词 | MUSCLE-CELL-PROLIFERATION ; MAMMALIAN HEPARANASE ; HEPARIN ; PROTEOGLYCANS ; INVOLVEMENT ; EXPRESSION ; RECEPTOR ; BINDING ; CLONING ; CANCER |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000240329400059 |
| 出版者 | AMER ASSOC CANCER RESEARCH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273502]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Ding, Jian |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Anti Tumor Pharmacol, Shanghai 201203, Peoples R China 2.Ocean Univ China, Dept Pharmacol & Glycobiol, Marine Drug & Food Inst, Qingdao, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhao, Huajun,Liu, Haiying,Chen, Yi,et al. Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting basic fibroblast growth factor, combats tumor angiogenesis and metastasis[J]. CANCER RESEARCH,2006,66(17):8779-8787. |
| APA | Zhao, Huajun.,Liu, Haiying.,Chen, Yi.,Xin, Xianliang.,Li, Jing.,...&Ding, Jian.(2006).Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting basic fibroblast growth factor, combats tumor angiogenesis and metastasis.CANCER RESEARCH,66(17),8779-8787. |
| MLA | Zhao, Huajun,et al."Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting basic fibroblast growth factor, combats tumor angiogenesis and metastasis".CANCER RESEARCH 66.17(2006):8779-8787. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。