Tumor targeting with a selective gelatinase inhibitor
| Autor: | Wadih Arap, Oula Penate Medina, Heli Valtanen, Erkki Ruoslahti, Pia Heikkilä, Tuula Salo, Renata Pasqualini, Erkki Koivunen, Carmela Kantor, Timo Sorsa, Yrjö T. Konttinen, Aija Rainisalo, Carl G. Gahmberg |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Phage display
Matrix metalloproteinase inhibitor Angiogenesis Gelatinase A Molecular Sequence Data Biomedical Engineering Mice Nude Bioengineering Antineoplastic Agents Matrix metalloproteinase Biology Matrix Metalloproteinase Inhibitors Applied Microbiology and Biotechnology Peptides Cyclic Metastasis 03 medical and health sciences Mice 0302 clinical medicine Peptide Library Neoplasms medicine Gelatinase Animals Humans Amino Acid Sequence Enzyme Inhibitors 030304 developmental biology DNA Primers 0303 health sciences Mice Inbred BALB C Base Sequence Neovascularization Pathologic Metalloendopeptidases medicine.disease Molecular biology 3. Good health Matrix Metalloproteinase 9 Tumor progression Gelatinases 030220 oncology & carcinogenesis Cancer research Molecular Medicine Matrix Metalloproteinase 2 Female Neoplasm Transplantation Biotechnology |
| Zdroj: | University of Helsinki |
| ISSN: | 1087-0156 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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