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Research Paper
Tissue Inhibitor of Metalloproteinases-2 Improves Antitumor Efficacy of a Replicating Adenovirus in Vivo
Myung-hee Kim, Thomas M. Bodenstine, Lucretia A Sumerel, Angel A Rivera, Andrew H Baker and Joanne T Douglas
volume 5 | issue 12
december 2006Pages: 1647 - 1653
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Clinical studies of replicating adenoviruses for the treatment of cancer have demonstrated their safety but have yielded disappointing results, indicating the need for new strategies to improve their efficacy. We hypothesized that the efficacy of a replicating adenovirus could be improved by expression of tissue inhibitor of metalloproteinases-2 (TIMP-2), a 21-kDa unglycosylated secretory protein. TIMP-2 specifically inhibits the active forms of a number of matrix metalloproteinases (MMPs) that play a role in the degradation of basement membranes and the extracellular matrix and are therefore involved in the control of the growth, invasion and metastasis of tumor cells, as well as angiogenesis. In addition, TIMP-2 can abrogate tumor growth and angiogenesis by a variety of mechanisms independent of MMP inhibition. In this study, we demonstrate that expression of TIMP-2 enhanced the antitumor efficacy of a replicating adenovirus in vivo, by reducing both tumor growth and angiogenesis.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.