HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Use of cell-SELEX to generate DNA aptamers as molecular probes of HPV-associated cervical cancer cells.

AbstractBACKGROUND:
Disease-specific biomarkers are an important tool for the timely and effective management of pathological conditions, including determination of susceptibility, diagnosis, and monitoring efficacy of preventive or therapeutic strategies. Aptamers, comprising single-stranded or double-stranded DNA or RNA, can serve as biomarkers of disease or biological states. Aptamers can bind to specific epitopes on macromolecules by virtue of their three dimensional structures and, much like antibodies, aptamers can be used to target specific epitopes on the basis of their molecular shape. The Systematic Evolution of Ligands by EXponential enrichment (SELEX) is the approach used to select high affinity aptamers for specific macromolecular targets from among the >10(13) oligomers comprising typical random oligomer libraries. In the present study, we used live cell-based SELEX to identify DNA aptamers which recognize cell surface differences between HPV-transformed cervical carcinoma cancer cells and isogenic, nontumorigenic, revertant cell lines.
METHODOLOGY/PRINCIPAL FINDINGS:
Whole-cell SELEX methodology was adapted for use with adherent cell lines (which we termed Adherent Cell-SELEX (AC-SELEX)). Using this approach, we identified high affinity aptamers (nanomolar range K(d)) to epitopes specific to the cell surface of two nontumorigenic, nontumorigenic revertants derived from the human cervical cancer HeLa cell line, and demonstrated the loss of these epitopes in another human papillomavirus transformed cervical cancer cell line (SiHa). We also performed preliminary investigation of the aptamer epitopes and their binding characteristics.
CONCLUSIONS/SIGNIFICANCE:
Using AC-SELEX we have generated several aptamers that have high affinity and specificity to the nontumorigenic, revertant of HPV-transformed cervical cancer cells. These aptamers can be used to identify new biomarkers that are related to carcinogenesis. Panels of aptamers, such as these may be useful in predicting the tumorigenic potential and properties of cancer biopsies and aid in the effective management of pathological conditions (diagnosis, predicted outcome, and treatment options).
AuthorsJessica C Graham, Helmut Zarbl
JournalPloS one (PLoS One) Vol. 7 Issue 4 Pg. e36103 ( 2012) ISSN: 1932-6203 [Electronic] United States
PMID22536456 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • DNA, Single-Stranded
  • Epitopes
  • Molecular Probes
Topics
  • Base Sequence
  • Binding Sites
  • Biomarkers, Tumor (chemistry, metabolism)
  • Cell Transformation, Viral
  • DNA, Single-Stranded (chemistry)
  • Epitopes
  • Female
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Molecular Probes (chemistry)
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Papillomavirus Infections (metabolism)
  • SELEX Aptamer Technique
  • Uterine Cervical Neoplasms (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: