Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting basic fibroblast growth factor, combats tumor angiogenesis and metastasis

doi:10.1158/0008-5472.CAN-06-1382

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting basic fibroblast growth factor, combats tumor angiogenesis and metastasis
	Zhao, Huajun ; Liu, Haiying ; Chen, Yi; Xin, Xianliang ; Li, Jing; Hou, Yongtai ; Zhang, Zhonghua ; Zhang, Xiongwen ; Me, Chengying ; Geng, Meiyu
刊名	CANCER RESEARCH
	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
出版者	AMER ASSOC CANCER RESEARCH
WOS记录号	WOS:000240329400059
内容类型	期刊论文
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.