BACKGROUND: Matrix metalloproteinases (MMP) are strongly associated with cancer progession. Broad-spectrum MMP inhibition is rarely beneficial clinically due to adverse effects. Of all MMPs, the gelatinases are associated with the spread of several types of cancer, including oral carcinoma. We have developed gelatinase-specific peptides, as well as their fusion with green fluorescent protein (GFP), capable of effectively targeting carcinomas. MATERIALS AND METHODS: Effects on tumor growth and lymphatic micrometastatic spread in vivo was studied by use of HSC-3-cell xenografted athymic nude mice. Antigelatinolytic mono- vs. polytherapies, as well as biological activity of peptide-GFP fusion, were also analyzed in vivo. RESULTS: Antigelatinolytic therapy effectively inhibited growth of xenografted tumors in mice but the proportion of enlarged lymph nodes remained the same; antigelatinolytic polytherapy seemed not to potentiate the antitumor effects. The peptide-GFP chimera sustained its activity in vivo and effectively homed to the primary tumors. CONCLUSION: Peptide gelatinase inhibitors are effective in inhibiting primary tumor growth but alone do not prevent the spread of carcinoma cells; however, their bioactive GFP fusion is a candidate for tumor characterization and imaging.
BACKGROUND: Matrix metalloproteinases (MMP) are strongly associated with cancer progession. Broad-spectrum MMP inhibition is rarely beneficial clinically due to adverse effects. Of all MMPs, the gelatinases are associated with the spread of several types of cancer, including oral carcinoma. We have developed gelatinase-specific peptides, as well as their fusion with green fluorescent protein (GFP), capable of effectively targeting carcinomas. MATERIALS AND METHODS: Effects on tumor growth and lymphatic micrometastatic spread in vivo was studied by use of HSC-3-cell xenografted athymic nude mice. Antigelatinolytic mono- vs. polytherapies, as well as biological activity of peptide-GFP fusion, were also analyzed in vivo. RESULTS: Antigelatinolytic therapy effectively inhibited growth of xenografted tumors in mice but the proportion of enlarged lymph nodes remained the same; antigelatinolytic polytherapy seemed not to potentiate the antitumor effects. The peptide-GFP chimera sustained its activity in vivo and effectively homed to the primary tumors. CONCLUSION: Peptide gelatinase inhibitors are effective in inhibiting primary tumor growth but alone do not prevent the spread of carcinoma cells; however, their bioactive GFP fusion is a candidate for tumor characterization and imaging.
Authors: Juho Suojanen; Niko Lehtonen; Esa Färkkilä; Jarkko Hietanen; Olli Teronen; Timo Sorsa; Jaana Hagström Journal: J Clin Diagn Res Date: 2014-09-20
Authors: Tanja-Maria Ranta; Juho Suojanen; Oula Peñate-Medina; Olga Will; Robert J Tower; Claus Glüer; Kalevi Kairemo; Carl G Gahmberg; Erkki Koivunen; Timo Sorsa; Per E J Saris; Justus Reunanen Journal: Mol Diagn Ther Date: 2014-02 Impact factor: 4.074