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. 2015 Dec;410(1-2):143-54.
doi: 10.1007/s11010-015-2546-4. Epub 2015 Aug 30.

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

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  4   5   6
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Holothurian glycosaminoglycan inhibits metastasis via inhibition of P-selectin in B16F10 melanoma cells

Zhiqiang Yue et al. Mol Cell Biochem. 2015 Dec.

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.

Keywords: Holothurian glycosaminoglycan; Melanoma; P-Selectin.

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