Anti-Heparanase Aptamers as Potential Diagnostic and Therapeutic Agents for Oral Cancer
| Autor: | Juha Risteli, Célia Martins Cortez, Suzanne Simmons, Paul Brenchley, Sotiris Missailidis, Hannaleena Jämsä, Tuula Salo, Carolina Cavalcante Bitu, Sirpa Salo, Sini Nurmenniemi, Edward A. McKenzie, Dilson Silva, Pia Nyberg, Carlos E. B. deAlmeida |
|---|---|
| Přispěvatelé: | Department of Oral and Maxillofacial Diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
lcsh:Medicine
MAMMALIAN HEPARANASE Biochemistry Synthetic Nucleic Acids Extracellular matrix 0302 clinical medicine Drug Stability DNA APTAMERS Nucleic Acids Molecular Cell Biology Drug Discovery Medicine and Health Sciences Cytotoxic T cell Biomacromolecule-Ligand Interactions Cytotoxicity lcsh:Science IN-VIVO FIBROBLAST-GROWTH-FACTOR Glucuronidase Mouth neoplasm 0303 health sciences Multidisciplinary Chemistry Aptamers Nucleotide Head and Neck Tumors 3. Good health Gene Expression Regulation Neoplastic Oncology LASER-DESORPTION/IONIZATION 030220 oncology & carcinogenesis Mouth Neoplasms Research Article Biotechnology EXPRESSION Drug Research and Development Aptamer education Biophysics 03 medical and health sciences In vivo Cell Line Tumor EXTRACELLULAR-MATRIX Humans Heparanase Neoplasm Invasiveness 030304 developmental biology Pharmacology lcsh:R Biology and Life Sciences Cancers and Neoplasms MASS-SPECTROMETRY Cell Biology CELL CARCINOMA Molecular biology 313 Dentistry PROTEIN INTERACTIONS Cell culture Cancer research lcsh:Q 3111 Biomedicine Clinical Medicine |
| Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 10, p e96846 (2014) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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