Anti-angiogenic and anti-tumor invasive activities of tissue inhibitor of metalloproteinase-3 from shark, Scyliorhinus torazame

• Published in: Biochimica et biophysica acta Vol. 1620; no. 1; pp. 59 - 64
• Main Authors: Kang, Jung A., Kim, Ji Tae, Song, Hyun Seok, Bae, Moon-Kyoung, Yi, Eui-Yeun, Kim, Kyu-Won, Kim, Yung-Jin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 17.03.2003
• Subjects: Angiogenesis; Angiogenesis Inhibitors - pharmacology; Animals; Aorta; Cancer; Cattle; Cell Movement - drug effects; Cells, Cultured; Down-Regulation; Endothelium - drug effects; Endothelium - metabolism; Fibrosarcoma; Fishes; Gelatinases - biosynthesis; Humans; Matrix Metalloproteinases - biosynthesis; MMP; Neoplasm Invasiveness; Sharks - genetics; Sharks - metabolism; TIMP; Tissue Inhibitor of Metalloproteinase-3 - biosynthesis; Tissue Inhibitor of Metalloproteinase-3 - genetics; Tissue Inhibitor of Metalloproteinase-3 - pharmacology; Transfection; Tumor Cells, Cultured; MMP; Angiogenesis; TIMP; Cancer
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/S0304-4165(02)00508-1

In order to investigate the anti-angiogenic activity of shark TIMP-3 (sTIMP-3) in endothelial cells, angiogenic assays including in vitro invasion assay, migration assay, zymogram assay and tube formation assay were performed. We observed that the overexpression of sTIMP-3 decreased the invasive capacity by about 70%, the migratory activity by about 50% and the production of gelatinase A in bovine aortic endothelial cells (BAECs). In addition, the overexpression of sTIMP-3 interfered with the formation of capillary-like network in endothelial cells. We also examined whether sTIMP-3 shows the anti-invasive activity in cancer cells. We found that the overexpression of sTIMP-3 diminished the invasive ability of the human fibrosarcoma HT1080 cells by about 40%. Also, the production of specific gelatinases was suppressed in the cancer cells. Therefore, we propose that sTIMP-3 acts as the inhibitor of angiogenesis in endothelial cells and the suppressor of tumor invasion in human fibrosarcoma HT1080 cells.