PUBLICATION
Holothurian glycosaminoglycan inhibits metastasis via inhibition of P-selectin in B16F10 melanoma cells
- Authors
- Yue, Z., Wang, A., Zhu, Z., Tao, L., Li, Y., Zhou, L., Chen, W., Lu, Y.
- ID
- ZDB-PUB-170214-129
- 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.
Citation
Yue, Z., Wang, A., Zhu, Z., Tao, L., Li, Y., Zhou, L., Chen, W., Lu, Y. (2015) Holothurian glycosaminoglycan inhibits metastasis via inhibition of P-selectin in B16F10 melanoma cells. Molecular and cellular biochemistry. 410:143-54.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping