Tumor targeting with a selective gelatinase inhibitor

Erkki Koivunen, Wadih Arap, Heli Valtanen, Aija Rainisalo, Oula Penate Medina, Pia Heikkilä, Carmela Kantor, Carl G. Gahmberg, Tuula Salo, Yrjö T. Konttinen, Timo Sorsa, Erkki Ruoslahti, Renata Pasqualini

Research output: Contribution to journalArticlepeer-review

482 Scopus citations


Several lines of evidence suggest that tumor growth, angiogenesis, and metastasis are dependent on matrix metalloproteinase (MMP) activity. However, the lack of inhibitors specific for the type IV collagenase/gelatinase family of MMPs has thus far prevented the selective targeting of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) for therapeutic intervention in cancer. Here, we describe the isolation of specific gelatinase inhibitors from phage display peptide libraries. We show that cyclic peptides containing the sequence HWGF are potent and selective inhibitors of MMP-2 and MMP-9 but not of several other MMP family members. Our prototype synthetic peptide, CTTHWGFTLC, inhibits the migration of human endothelial cells and tumor cells. Moreover, it prevents tumor growth and invasion in animal models and improves survival of mice bearing human tumors. Finally, we show that CTTHWGFTLC-displaying phage specifically target angiogenic blood vessels in vivo. Selective gelatinase inhibitors may prove useful in tumor targeting and anticancer therapies.

Original languageEnglish (US)
Pages (from-to)768-774
Number of pages7
JournalNature biotechnology
Issue number8
StatePublished - Aug 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering


  • Angiogenesis
  • Cancer therapy
  • Matrix metalloproteinase
  • Phage display
  • Tumor targeting

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