Holothurian glycosaminoglycan inhibits metastasis via inhibition of P-selectin in B16F10 melanoma cells
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  • 作者:Zhiqiang Yue ; Aiyun Wang ; Zhijie Zhu ; Li Tao ; Yao Li…
  • 关键词:Holothurian glycosaminoglycan ; P ; Selectin ; Melanoma
  • 刊名:Molecular and Cellular Biochemistry
  • 出版年:2015
  • 出版时间:December 2015
  • 年:2015
  • 卷:410
  • 期:1-2
  • 页码:143-154
  • 全文大小:4,773 KB
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  • 作者单位:Zhiqiang Yue (1)
    Aiyun Wang (1) (2) (3)
    Zhijie Zhu (1)
    Li Tao (1)
    Yao Li (1)
    Liang Zhou (1)
    Wenxing Chen (1) (2) (3)
    Yin Lu (1) (2) (3)

    1. 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
    2. Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing, 210023, China
    3. Jiangsu Provincial Center for Research and Development of Marine Drugs, Nanjing, 210023, Jiangsu, China
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Life Sciences
    Biochemistry
    Medical Biochemistry
    Oncology
    Cardiology
  • 出版者:Springer Netherlands
  • ISSN:1573-4919
文摘
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. Keywords Holothurian glycosaminoglycan P-Selectin Melanoma

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