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Suppressive Mechanism of Salmosin, a Novel Disintegrin in B16 Melanoma Cell Metastasis

https://doi.org/10.1006/bbrc.2000.3130Get rights and content

Abstract

We have previously reported that salmosin, a novel disintegrin, was isolated from Korean snake (Agkistrodon halys brevicaudus) venom and significantly inhibited solid tumor growth in mice by perturbation of tumor-specific angiogenesis via blocking αvβ3 integrin expressed on vascular endothelial cells. In this study, we investigated the functional specificity of salmosin in tumor cell metastasis. Recombinant salmosin expressed in E. coli that has the RGD sequence markedly inhibited both B16F10 melanoma cell adhesion to the extracellular matrix proteins as well as B16F10 melanoma cell invasion through Matrigel-coated filter. The inhibition by salmosin can be caused by blocking integrins expressed on the surface of B16F10 melanoma cells. Salmosin significantly inhibited the proliferation of B16F10 melanoma cells on the plate coated with collagen I in a dose-dependent manner. In vivo B16F10 melanoma experimental metastasis, salmosin showed remarkable significant inhibitory effect on lung tumor colonization in a concentration-dependent manner. These results clearly demonstrate that antimetastatic activity of salmosin resulted from blocking the integrin-mediated adherence and αvβ3 integrin-mediated proliferation of the melanoma cells.

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    Citation Excerpt :

    Salmosin treatment on melanoma cells inhibited cell adhesion and induced integrin-dependent apoptosis. It also lowered the tumor-induced angiogenesis, metastasis, and induced morphological changes suggesting the role of FAK in regulating these pathways (Chung et al., 2010; Hong et al., 2003; Kang et al., 1999, 2000; Shin et al., 2003). Disba-01 in nM concentration modulated MMP-2 and MMP-9 production with inhibitory effects on cell migration, angiogenesis, and metastasis in endothelial cells in vivo (Selistre-de-Araujo et al., 2010).

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Abbreviations used: PBS, phosphate-buffered saline; EDTA, ethylenediaminetetraacetic acid; ECM, extracellular matrix; RGD, arginyl-glycyl-aspartic acid.

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