Holothurian glycosaminoglycan inhibits metastasis via inhibition of P-selectin in B16F10 melanoma cells

Molecular and Cellular Biochemistry
Zhiqiang YueYin Lu

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.

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Citations

Mar 24, 2020·Integrative Cancer Therapies·Cunzhi LinLiyan Shen
May 5, 2018·International Journal of Molecular Sciences·Yuri Khotimchenko
May 6, 2016·Frontiers in Oncology·Alessandro NatoniMichael E O'Dwyer
Jan 1, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Kailong WangHaiyang Yu

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