caa a22 4500 606236015 CHVBK 20210128101245.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s11010-015-2546-4 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2546-4 Holothurian glycosaminoglycan inhibits metastasis via inhibition of P-selectin in B16F10 melanoma cells [Elektronische Daten] [Zhiqiang Yue, Aiyun Wang, Zhijie Zhu, Li Tao, Yao Li, Liang Zhou, Wenxing Chen, Yin Lu] P-selectin-mediated tumor cell adhesion to platelets is a well-established stage in the process of tumor metastasis. Through computerized structural analysis, we found a marine-derived polysaccharide, holothurian glycosaminoglycan (hGAG), behaved as a ligand-competitive inhibitor of P-selectin, indicating its potential to disrupt the binding of P-selectin to cell surface receptor and activation of downstream regulators of tumor cell migration. Our experimental data demonstrated that hGAG significantly inhibited P-selectin-mediated adhesion of tumor cells to platelets and tumor cell migration in vitro and reduced subsequent pulmonary metastasis in vivo. Furthermore, abrogation of the P-selectin-mediated adhesion of tumor cells led to down-regulation of protein levels of integrins, FAK and MMP-2/9 in B16F10 cells, which is a crucial molecular mechanism of hGAG to inhibit tumor metastasis. In conclusion, hGAG has emerged as a novel anti-cancer agent via blocking P-selectin-mediated malignant events of tumor metastasis. Springer Science+Business Media New York, 2015 Holothurian glycosaminoglycan nationallicence P-Selectin nationallicence Melanoma nationallicence Yue Zhiqiang College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut Wang Aiyun College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut Zhu Zhijie College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut Tao Li College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut Li Yao College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut Zhou Liang College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut Chen Wenxing College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut Lu Yin College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 410/1-2(2015-12-01), 143-154 0300-8177 410:1-2<143 2015 410 11010 https://doi.org/10.1007/s11010-015-2546-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2546-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yue Zhiqiang College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Wang Aiyun College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Zhu Zhijie College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Tao Li College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Li Yao College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Zhou Liang College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Chen Wenxing College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Lu Yin College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210023, Nanjing, Jiangsu, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 410/1-2(2015-12-01), 143-154 0300-8177 410:1-2<143 2015 410 11010