Selective inhibition of matrix metalloproteinase-14 blocks tumor growth, invasion, and angiogenesis.

Published

Journal Article

Inhibition of specific matrix metalloproteinases (MMP) is an attractive noncytotoxic approach to cancer therapy. MMP-14, a membrane-bound zinc endopeptidase, has been proposed to play a central role in tumor growth, invasion, and neovascularization. Besides cleaving matrix proteins, MMP-14 activates proMMP-2 leading to an amplification of pericellular proteolytic activity. To examine the contribution of MMP-14 to tumor growth and angiogenesis, we used DX-2400, a highly selective fully human MMP-14 inhibitory antibody discovered using phage display technology. DX-2400 blocked proMMP-2 processing on tumor and endothelial cells, inhibited angiogenesis, and slowed tumor progression and formation of metastatic lesions. The combination of potency, selectivity, and robust in vivo activity shows the potential of a selective MMP-14 inhibitor for the treatment of solid tumors.

Full Text

Duke Authors

Cited Authors

  • Devy, L; Huang, L; Naa, L; Yanamandra, N; Pieters, H; Frans, N; Chang, E; Tao, Q; Vanhove, M; Lejeune, A; van Gool, R; Sexton, DJ; Kuang, G; Rank, D; Hogan, S; Pazmany, C; Ma, YL; Schoonbroodt, S; Nixon, AE; Ladner, RC; Hoet, R; Henderikx, P; Tenhoor, C; Rabbani, SA; Valentino, ML; Wood, CR; Dransfield, DT

Published Date

  • February 10, 2009

Published In

Volume / Issue

  • 69 / 4

Start / End Page

  • 1517 - 1526

PubMed ID

  • 19208838

Pubmed Central ID

  • 19208838

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

International Standard Serial Number (ISSN)

  • 0008-5472

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.can-08-3255

Language

  • eng