title: Holothurian glycosaminoglycan inhibits metastasis via inhibition of P-selectin in B16F10 melanoma cells.
abstract: 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.
authors: College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, Jiangsu, China.
authors: Zhiqiang
authors: Z
authors: Yue
authors: College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, Jiangsu, China.|Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing, 210023, China.|Jiangsu Provincial Center for Research and Development of Marine Drugs, Nanjing, 210023, Jiangsu, China.
authors: Aiyun
authors: A
authors: Wang
authors: College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, Jiangsu, China.
authors: Zhijie
authors: Z
authors: Zhu
authors: College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, Jiangsu, China.
authors: Li
authors: L
authors: Tao
authors: College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, Jiangsu, China.
authors: Yao
authors: Y
authors: Li
authors: College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, Jiangsu, China.
authors: Liang
authors: L
authors: Zhou
authors: College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, Jiangsu, China.|Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing, 210023, China.|Jiangsu Provincial Center for Research and Development of Marine Drugs, Nanjing, 210023, Jiangsu, China.
authors: Wenxing
authors: W
authors: Chen
authors: College of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, Jiangsu, China. profyinlu@163.com.|Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing, 210023, China. profyinlu@163.com.|Jiangsu Provincial Center for Research and Development of Marine Drugs, Nanjing, 210023, Jiangsu, China. profyinlu@163.com.
authors: Yin
authors: Y
authors: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006025:Glycosaminoglycans / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D047332:Holothuria / Q000737:chemistry; D016023:Integrins / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008810:Mice, Inbred C57BL; D062105:Molecular Docking Simulation; D009361:Neoplasm Invasiveness; D019007:P-Selectin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D015398:Signal Transduction / Q000187:drug effects; D015027:Zebrafish
chemical_list: D000970:Antineoplastic Agents; D006025:Glycosaminoglycans; D016023:Integrins; D019007:P-Selectin; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Holothurian glycosaminoglycan; Melanoma; P-Selectin