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.
Kang
I C
IC
Department of Oncology, Kyunghee University, Seoul, 130-701, Korea.
Kim
D S
DS
Jang
Y
Y
Chung
K H
KH
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003435:Crotalid Venoms / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use*; D019483:Disintegrins / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006651:Histocytochemistry; D007797:Laminin / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000032:analysis; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011509:Proteoglycans / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003435:Crotalid Venoms; D019483:Disintegrins; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins; D007797:Laminin; D009842:Oligopeptides; D010446:Peptide Fragments; D011509:Proteoglycans; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; C115393:salmosin; C059485:matrigel; C047981:arginyl-glycyl-aspartic acid; D003094:Collagen