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

 In-Cheol Kang  ;  Doo-Sik Kim  ;  Yangsoo Jang  ;  Kwang-Hoe Chung 
 Biochemical and Biophysical Research Communications, Vol.275(1) : 169-173, 2000 
Journal Title
 Biochemical and Biophysical Research Communications 
Issue Date
Animals ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Cell Adhesion/drug effects ; Cell Division/drug effects ; Collagen/metabolism ; Crotalid Venoms/chemistry ; Crotalid Venoms/genetics ; Crotalid Venoms/pharmacology* ; Crotalid Venoms/therapeutic use* ; Disintegrins/genetics ; Disintegrins/pharmacology* ; Disintegrins/therapeutic use* ; Dose-Response Relationship, Drug ; Drug Combinations ; Extracellular Matrix Proteins/metabolism ; Histocytochemistry ; Laminin/metabolism ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology ; Lung Neoplasms/secondary ; Melanoma, Experimental/drug therapy* ; Melanoma, Experimental/metabolism ; Melanoma, Experimental/pathology* ; Mice ; Mice, Inbred C57BL ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Oligopeptides/analysis ; Peptide Fragments/chemistry ; Peptide Fragments/pharmacology ; Peptide Fragments/therapeutic use ; Proteoglycans/metabolism ; Receptors, Vitronectin/antagonists & inhibitors ; Receptors, Vitronectin/metabolism ; Recombinant Proteins/chemistry ; Recombinant Proteins/pharmacology ; Recombinant Proteins/therapeutic use ; Tumor Cells, Cultured
disintegrin ; salmosin ; tumor metastasis ; snake venom
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 alphavbeta3 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 alphavbeta3 integrin-mediated proliferation of the melanoma cells.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
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