Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase 2

Y. M. Kim, J. W. Jang, O. H. Lee, J. Yeon, E. Y. Choi, K. W. Kim, S. T. Lee, Y. G. Kwon

Research output: Contribution to journalArticle

290 Citations (Scopus)

Abstract

Here we report the inhibition of cellular invasion by a recombinant mouse endostatin and the possible mechanism of the inhibition. Endostatin significantly reduced endothelial as well as tumor cellular invasion into the reconstituted basement membrane in vitro. Gelatin zymographic analysis revealed that the activation of promatrix metalloproteinase-2 (proMMP-2) that was secreted from endothelial cells was blocked upon endostatin treatment. Studies with recombinant MMPs confirmed that endostatin inhibited proMMP-2 activation, mediated by both membrane-type 1 MMP and 4-aminophenylmercuric acetate. Furthermore, enzymatic assays using a peptide substrate demonstrated that endostatin inhibited the catalytic activities of both MMP-2 and membrane-type 1 MMP. Finally, coimmunoprecipitation experiments revealed that endostatin formed a stable complex with proMMP-2. These novel findings would, at least in part, explain the mechanism of the potent antiangiogenic and antitumor activities of endostatin.

Original languageEnglish
Pages (from-to)5410-5413
Number of pages4
JournalCancer Research
Volume60
Issue number19
Publication statusPublished - 2000 Oct 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase 2'. Together they form a unique fingerprint.

  • Cite this