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ZFIN ID: ZDB-PUB-170214-129
Holothurian glycosaminoglycan inhibits metastasis via inhibition of P-selectin in B16F10 melanoma cells
Yue, Z., Wang, A., Zhu, Z., Tao, L., Li, Y., Zhou, L., Chen, W., Lu, Y.
Date: 2015
Source: Molecular and cellular biochemistry 410: 143-54 (Journal)
Registered Authors:
Keywords: Holothurian glycosaminoglycan, Melanoma, P-Selectin
MeSH Terms:
  • Animals
  • Antineoplastic Agents/chemistry
  • Antineoplastic Agents/isolation & purification
  • Antineoplastic Agents/metabolism
  • Antineoplastic Agents/pharmacology*
  • Cell Line, Tumor
  • Cell Movement/drug effects*
  • Dose-Response Relationship, Drug
  • Female
  • Focal Adhesion Kinase 1/metabolism
  • Glycosaminoglycans/chemistry
  • Glycosaminoglycans/isolation & purification
  • Glycosaminoglycans/metabolism
  • Glycosaminoglycans/pharmacology*
  • Holothuria*/chemistry
  • Integrins/metabolism
  • Lung Neoplasms/genetics
  • Lung Neoplasms/metabolism
  • Lung Neoplasms/prevention & control*
  • Lung Neoplasms/secondary
  • Matrix Metalloproteinase 2/metabolism
  • Matrix Metalloproteinase 9/metabolism
  • Melanoma, Experimental/drug therapy*
  • Melanoma, Experimental/genetics
  • Melanoma, Experimental/metabolism
  • Melanoma, Experimental/secondary
  • Mice, Inbred C57BL
  • Molecular Docking Simulation
  • Neoplasm Invasiveness
  • P-Selectin/antagonists & inhibitors*
  • P-Selectin/chemistry
  • P-Selectin/genetics
  • P-Selectin/metabolism
  • Protein Binding
  • Protein Conformation
  • Signal Transduction/drug effects
  • Zebrafish
PubMed: 26318439 Full text @ Mol. Cell. Biochem.
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.