Anti-heparanase aptamers as potential diagnostic and therapeutic agents for oral cancer

Suzanne C. Simmons, Hannaleena Jämsä, Dilson Silva, Celia M. Cortez, Edward A. McKenzie, Carolina C. Bitu, Sirpa Salo, Sini Nurmenniemi, Pia Nyberg, Juha Risteli, Carlos E B De Almeida, Paul E C Brenchley, Tuula Salo, Sotiris Missailidis

    Research output: Contribution to journalArticlepeer-review

    Abstract

    © 2014 Simmons et al.Heparanase is an endoglycosidase enzyme present in activated leucocytes, mast cells, placental tissue, neutrophils and macrophages, and is involved in tumour metastasis and tissue invasion. It presents a potential target for cancer therapies and various molecules have been developed in an attempt to inhibit the enzymatic action of heparanase. In an attempt to develop a novel therapeutic with an associated diagnostic assay, we have previously described high affinity aptamers selected against heparanase. In this work, we demonstrated that these anti-heparanase aptamers are capable of inhibiting tissue invasion of tumour cells associated with oral cancer and verified that such inhibition is due to inhibition of the enzyme and not due to other potentially cytotoxic effects of the aptamers. Furthermore, we have identified a short 30 bases aptamer as a potential candidate for further studies, as this showed a higher ability to inhibit tissue invasion than its longer counterpart, as well as a reduced potential for complex formation with other non-specific serum proteins. Finally, the aptamer was found to be stable and therefore suitable for use in human models, as it showed no degradation in the presence of human serum, making it a potential candidate for both diagnostic and therapeutic use.
    Original languageEnglish
    Article numbere96846
    JournalPLoS ONE
    Volume9
    Issue number10
    DOIs
    Publication statusPublished - 8 Oct 2014

    Research Beacons, Institutes and Platforms

    • Manchester Institute of Biotechnology

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