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Anti-tumorigenic and Invasive Activity of Colon Cancer Cells Transfected with the Retroviral Vector Encoding Tissue Inhibitor of Metalloproteinase-2  

오일웅 (식품의약품안전청 생명공학의약품과)
정자영 (식품의약품안전청 생명공학의약품)
장석기 (식품의약품안전청 생명공학의약품)
이수해 (식품의약품안전청 생명공학의약품)
김연수 (배제대학)
손여원 (식품의약품안전청 생명공학의약품과)
Publication Information
YAKHAK HOEJI / v.48, no.3, 2004 , pp. 189-196 More about this Journal
Abstract
Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) playa key role in tumor invasion and metastasis. As an inhibitor of MMP-2, TIMP-2 is known to block both the invasive and metastatic behavior of cancer cells, and decrease tumor growth activity. We performed this study to investigate the effects of TIMP-2 over-expression induced by retroviral mediated gene transfer in vitro and in vivo. The human colon cancer cell line SW480 was transfected with the retroviral vector encoding TIMP-2. The effects of TIMP-2 over-expression were analyzed by invasion assay and gelatinase activity test in colon cancer cells and tumorigencity in nude mice. In evaluation of the transfection efficiency of the retroviral vector encoding TIMP-2 in colon cancer cells, we confirmed up-regulation of TIMP-2 expression dependent on the time of cell culture. In addition, inhibition of MMP-2 expression in SW480/TIMP-2 was shown by gelatin zymography. In the in vitro invasion assay SW480/TIMP-2 inhibited the invasiveness on matrigel coated with collagen. To determine whether TIMP-2 can modulate in vivo tumorigenicity and metastasis, SW480/TIMP-2 cells were injected subcutaneously in nude mice. The tumor mass formation of SW480/TIMP-2 cells in nude mice was markedly decreased compared to nontransfected cancer cells. These results showed that colon cancer cells transfected with the retroviral vector encoding TIMP-2 inhibits the invasiveness in vitro and tumorigenicity in vivo.
Keywords
MMP-2; TIMP-2; retroviral vector; tumorigenicity; colon cancer cell; nude mice;
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