Suppressive Mechanism of Salmosin, a Novel Disintegrin in B16 Melanoma Cell Metastasis
Copyright policy )Suppressive Mechanism of Salmosin, a Novel Disintegrin in B16 Melanoma Cell Metastasis
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.
- Kyung Hee University Korea (Republic of)
- Yonsei University Medical Library Korea (Republic of)
- Yonsei University Korea (Republic of)
- Yonsei University Health System Korea (Republic of)
Experimental/drug therapy*, Lung Neoplasms, Disintegrins, Melanoma, Experimental, Recombinant Proteins/chemistry, Inbred C57BL, Vitronectin/metabolism, Mice, Recombinant Proteins/therapeutic use, Antineoplastic Agents/chemistry, Receptors, Lung Neoplasms/pathology, Cell Adhesion/drug effects, Recombinant Proteins/pharmacology, Disintegrins/genetics, Melanoma, Disintegrins/pharmacology*, Extracellular Matrix Proteins, Cultured, Histocytochemistry, Vitronectin/antagonists & inhibitors, Crotalid Venoms/therapeutic use*, Tumor Cells, disintegrin, Experimental/pathology*, Drug Combinations, Collagen, Drug, Antineoplastic Agents/pharmacology, Oligopeptides, Cell Division, 570, Peptide Fragments/chemistry, Cell Division/drug effects, 610, Antineoplastic Agents, Extracellular Matrix Proteins/metabolism, Dose-Response Relationship, Crotalid Venoms/pharmacology*, Collagen/metabolism, Oligopeptides/analysis, Crotalid Venoms, Cell Adhesion, Crotalid Venoms/genetics, Animals, Neoplasm Invasiveness, Lung Neoplasms/secondary, Experimental/metabolism, Lung Neoplasms/drug therapy, Crotalid Venoms/chemistry, Disintegrins/therapeutic use*, Peptide Fragments/therapeutic use, Peptide Fragments/pharmacology, Dose-Response Relationship, Drug, Antineoplastic Agents/therapeutic use, Proteoglycans/metabolism, Peptide Fragments, Laminin/metabolism, Mice, Inbred C57BL, salmosin, Laminin, Neoplasm Transplantation
Experimental/drug therapy*, Lung Neoplasms, Disintegrins, Melanoma, Experimental, Recombinant Proteins/chemistry, Inbred C57BL, Vitronectin/metabolism, Mice, Recombinant Proteins/therapeutic use, Antineoplastic Agents/chemistry, Receptors, Lung Neoplasms/pathology, Cell Adhesion/drug effects, Recombinant Proteins/pharmacology, Disintegrins/genetics, Melanoma, Disintegrins/pharmacology*, Extracellular Matrix Proteins, Cultured, Histocytochemistry, Vitronectin/antagonists & inhibitors, Crotalid Venoms/therapeutic use*, Tumor Cells, disintegrin, Experimental/pathology*, Drug Combinations, Collagen, Drug, Antineoplastic Agents/pharmacology, Oligopeptides, Cell Division, 570, Peptide Fragments/chemistry, Cell Division/drug effects, 610, Antineoplastic Agents, Extracellular Matrix Proteins/metabolism, Dose-Response Relationship, Crotalid Venoms/pharmacology*, Collagen/metabolism, Oligopeptides/analysis, Crotalid Venoms, Cell Adhesion, Crotalid Venoms/genetics, Animals, Neoplasm Invasiveness, Lung Neoplasms/secondary, Experimental/metabolism, Lung Neoplasms/drug therapy, Crotalid Venoms/chemistry, Disintegrins/therapeutic use*, Peptide Fragments/therapeutic use, Peptide Fragments/pharmacology, Dose-Response Relationship, Drug, Antineoplastic Agents/therapeutic use, Proteoglycans/metabolism, Peptide Fragments, Laminin/metabolism, Mice, Inbred C57BL, salmosin, Laminin, Neoplasm Transplantation
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