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Inhibition of angiogenesis by salmosin expressed in vitro.

Abstract
Recently, salmosin, a novel snake venom-derived disintegrin containing the Arg-Gly-Asp (RGD) sequence, was reported to be both antiangiogenic and antitumorigenic. The antitumor activity was substantiated by in vivo administration of recombinant salmosin into mice bearing tumors. However, it was difficult to prepare functionally active recombinant salmosin and to maintain a therapeutically effective concentration of the protein in the circulatory system by daily injections. Hence, we have suggested that salmosin gene transfer mediated by cationic liposomes may be a practical alternative for cancer treatment. Plasmids encoding the salmosin gene were constructed and then transferred by means of cationic liposomes into transformed human embryonic kidney (HEK) 293 cells. The transfected genes were able to produce functionally active salmosin proteins in vitro. In fact, the expressed salmosin remarkably inhibited proliferation of bovine capillary endothelial (BCE) cells and effectively inhibited the migration of highly metastatic B16BL6 mouse melanoma cells. Neovascularization in chick chorio-allantoic membranes (CAM) and in Matrigel implanted subcutaneously into mice was greatly inhibited in the presence of the expressed salmosin. Based on these experimental results, we suggest that the antitumor effect induced by salmosin gene transfection may be due to the antiangiogenic activity of the expressed salmosin proteins.
AuthorsSoo In Kim, Keun Sik Kim, Hong Sung Kim, Myoung Min Choi, Doo Sik Kim, Kwang Hoe Chung, Yong Serk Park
JournalOncology research (Oncol Res) Vol. 14 Issue 4-5 Pg. 227-33 ( 2004) ISSN: 0965-0407 [Print] United States
PMID14977354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiogenesis Inhibitors
  • Crotalid Venoms
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • salmosin
  • Fibroblast Growth Factor 2
  • matrigel
  • Collagen
Topics
  • Angiogenesis Inhibitors (genetics, metabolism)
  • Animals
  • Cattle
  • Cell Division (drug effects)
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement
  • Chickens
  • Chorion (blood supply, metabolism)
  • Collagen
  • Crotalid Venoms (genetics, metabolism)
  • Drug Combinations
  • Endothelial Cells (cytology, drug effects, metabolism)
  • Fibroblast Growth Factor 2 (pharmacology)
  • Gene Expression
  • Humans
  • Laminin
  • Melanoma (genetics, pathology)
  • Mice
  • Proteoglycans
  • Transfection

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