title: Anti-heparanase aptamers as potential diagnostic and therapeutic agents for oral cancer.
abstract: 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.
authors.affiliation: Department of Chemistry and Analytical Sciences, The Open University, Milton Keynes, United Kingdom.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Simmons
authors.affiliation: Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland; Medical Research Center and Oulu University Hospital, Oulu, Finland.
authors.forename: Hannaleena
authors.initials: H
authors.lastname: Jämsä
authors.affiliation: Institute of Mathematics and Statistics, Rio de Janeiro State University, Rio de Janeiro, Brazil.
authors.forename: Dilson
authors.initials: D
authors.lastname: Silva
authors.affiliation: Institute of Mathematics and Statistics, Rio de Janeiro State University, Rio de Janeiro, Brazil.
authors.forename: Celia M
authors.initials: CM
authors.lastname: Cortez
authors.affiliation: Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom.
authors.forename: Edward A
authors.initials: EA
authors.lastname: McKenzie
authors.affiliation: Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland; Medical Research Center and Oulu University Hospital, Oulu, Finland.
authors.forename: Carolina C
authors.initials: CC
authors.lastname: Bitu
authors.affiliation: Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Salo
authors.affiliation: Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland.
authors.forename: Sini
authors.initials: S
authors.lastname: Nurmenniemi
authors.affiliation: Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland; Medical Research Center and Oulu University Hospital, Oulu, Finland.
authors.forename: Pia
authors.initials: P
authors.lastname: Nyberg
authors.affiliation: Institute of Diagnostics, Department of Clinical Chemistry, University of Oulu, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Risteli
authors.affiliation: Department of Chemistry and Analytical Sciences, The Open University, Milton Keynes, United Kingdom; Laboratório de Radiobiologia, Instituto de Radioproteção e Dosimetria, Rio de Janeiro, Brazil.
authors.forename: Carlos E B
authors.initials: CE
authors.lastname: deAlmeida
authors.affiliation: Renal Research Group, University of Manchester, Manchester, United Kingdom.
authors.forename: Paul E C
authors.initials: PE
authors.lastname: Brenchley
authors.affiliation: Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland; Medical Research Center and Oulu University Hospital, Oulu, Finland; Graduate Program in Estomatopatologia, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil; Institute of Dentistry, University of Helsinki, Helsinki, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Sotiris
authors.initials: S
authors.lastname: Missailidis
mesh_terms: D052157:Aptamers, Nucleotide / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004355:Drug Stability; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009361:Neoplasm Invasiveness; D000099175:Heparanase
chemical_list: D052157:Aptamers, Nucleotide; D005966:Glucuronidase; D000099175:Heparanase