Abstract 883: Cell-based selection of RNA-aptamers to specifically target glioblastoma cancer stem cells

Abstract

Abstract Stem cells are a group of cells, which have two important fundamental properties: self-renewal and multipotency. Stem cells have been identified also in many human cancers on the basis of being both morphologically and functionally distinct from other cells within the heterogeneous tumor mass. According to “cancer stem cell hypothesis,” the cancer stem cells (CSC) would remain unaffected by conventional therapies, and capable of repopulating the tumor and giving rise to cancer recurrence. The possibility to identify highly selective biomarkers on CSC would greatly improve cancer diagnosis and treatment. Recently, nucleic acid-based aptamers have proven useful as reagents for identifying cell surface proteins and for cell typing. Further, their high specificity and low toxicity render them a valid alternative to antibodies for in vivo cell recognition. We have developed the SELEX technology on intact glioblastoma cancer stem cells to generate aptamers as biologically active high affinity ligands for CSC-specific cell surface proteins. The approach has been applied by utilizing glioblastoma differentiated tumor cells as a negative selection, and cancer stem cells obtained from two different patients, as positive selection. Upon 16 cycles of SELEX, we generated a set of 2′-fluoro-pyrimidines containing RNA aptamers that, based on sequence analysis, have been grouped into 5 main families. Best aptamers have been then selected by binding experiments for their ability to distinguish glioblastoma CSC from differentiated tumor cells. We thus determined the binding affinity of each molecule to the cell surface specific targets. Functional experiments will be as well presented to further insight the biological role of the most promising aptamer molecules in the acquisition and maintenance of stem cells properties of glioma cancer cells. Results demonstrate the possibility to generate RNA-based aptamers as potential innovative tools for the selective targeting of cancer stem cells. A proteomic approach will define the specific membrane targets of the selected aptamers Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 883. doi:1538-7445.AM2012-883