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Oligosaccharides from fucosylated glycosaminoglycan prevent breast cancer metastasis in mice by inhibiting heparanase activity and angiogenesis
Zhou,Lutan; Yin,Ronghua; Gao,Na; Sun,Huifang; Chen,Dingyuan; Cai,Ying; Ren,Lin; Yang,Lian; Zuo,Zhili; Zhang,Hongbin; Zhao,Jinhua
2021
Source PublicationPHARMACOLOGICAL RESEARCH
ISSN1043-6618
Volume166Pages:105527
AbstractThe invasion and metastasis of tumor cells are the hallmarks of malignant diseases and the greatest obstacle to overcome. Heparanase-mediated degradation of heparan sulfate (HS) is the critical process for tumor angiogenesis and metastasis, therefore, heparanase become an attractive target for cancer research. Herein, we reported a native fucosylated glycosaminoglycan (nHG) extracted from sea cucumber Holothuria fuscopunctata and a depolymerized nHG (dHG) and its contained oligosaccharides (hs17, hs14, hs11, hs8 and hs5), acting as heparanase inhibitors. nHG and its derivatives have the ability to bind with heparanase directly, leading to significant inhibition of heparanase activity. Moreover, their apparent binding affinity to heparanase was comparable to their inhibitory effect, which was elevated along with the increase of chain length, similar to the effect of heparins. In addition, oligosaccharides inhibited the migration and invasion of 4T1 mammary carcinoma cells and human umbilical vein endothelial cells (HUVECs) and also suppressed tube formation in Matrigel matrix and angiogenesis in the chick chorioallantoic membrane (CAM) assay. In the metastatic mouse model, oligosaccharides exhibited practical antimetastatic effects on 4T1 mammary carcinoma cells. According to the reported anticoagulant activity and the low bleeding tendency of dHG and its oligosaccharides, the use of the oligosaccharides may lead to better effects on tumor patients with thrombosis tendency.
KeywordOligosaccharides Heparanase Angiogenesis Metastasis FIBROBLAST-GROWTH-FACTOR TUMOR-GROWTH SULFATE PROTEOGLYCANS MAMMALIAN HEPARANASE COMBINATION MECHANISMS DISCOVERY BINDING TARGET PI-88
DOI10.1016/j.phrs.2021.105527
WOS IDWOS:000643656100040
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/72999
Collection中国科学院昆明植物研究所
Affiliation1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, 132 Lanhei Rd, Kunming 650201, Yunnan, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Yunnan Univ, Sch Chem Sci & Technol, Key Lab Med Chem Nat Resource, Minist Educ & Yunnan Prov, Kunming 650091, Yunnan, Peoples R China
4.South Cent Univ Nationalities, Sch Pharmaceut Sci, 182 Minzu Rd Hongshan Dist, Wuhan 430074, Peoples R China
Recommended Citation
GB/T 7714
Zhou,Lutan,Yin,Ronghua,Gao,Na,et al. Oligosaccharides from fucosylated glycosaminoglycan prevent breast cancer metastasis in mice by inhibiting heparanase activity and angiogenesis[J]. PHARMACOLOGICAL RESEARCH,2021,166:105527.
APA Zhou,Lutan.,Yin,Ronghua.,Gao,Na.,Sun,Huifang.,Chen,Dingyuan.,...&Zhao,Jinhua.(2021).Oligosaccharides from fucosylated glycosaminoglycan prevent breast cancer metastasis in mice by inhibiting heparanase activity and angiogenesis.PHARMACOLOGICAL RESEARCH,166,105527.
MLA Zhou,Lutan,et al."Oligosaccharides from fucosylated glycosaminoglycan prevent breast cancer metastasis in mice by inhibiting heparanase activity and angiogenesis".PHARMACOLOGICAL RESEARCH 166(2021):105527.
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