Anti-angiogenic and anti-tumor invasive activities of tissue inhibitor of metalloproteinase-3 from shark, Scyliorhinus torazame.
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.
Kang
Jung A
JA
Department of Molecular Biology, Pusan National University, South Korea.
Kim
Ji Tae
JT
Song
Hyun Seok
HS
Bae
Moon-Kyoung
MK
Yi
Eui-Yeun
EY
Kim
Kyu-Won
KW
Kim
Yung-Jin
YJ
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism*; D005354:Fibrosarcoma; D005399:Fishes; D018093:Gelatinases / Q000096:biosynthesis; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D012754:Sharks / Q000235:genetics / Q000378:metabolism*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D019717:Tissue Inhibitor of Metalloproteinase-3; D018093:Gelatinases; D020782:Matrix Metalloproteinases