title: RNA aptamer against a cancer stem cell marker epithelial cell adhesion molecule.
abstract: The lack of a specific targeting strategy against cancer stem cells in current cancer treatment regimens is at least partly responsible for life-threatening cytotoxicity for patients undergoing traditional chemotherapy. An effective cancer stem cell targeting system is urgently required for the next generation of cancer medicine. Epithelial cell adhesion molecule (EpCAM) is overexpressed in most solid cancers and it has recently been identified as a cancer stem cell marker. In this study, we isolated a 40-base RNA aptamer that binds to EpCAM from a random oligonucleotide library using systematic evolution of ligands by exponential enrichment. The aptamer was further truncated to 19 bases. This 19-nt RNA aptamer interacts specifically with a number of live human cancer cells derived from breast, colorectal, and gastric cancers that express EpCAM, but not with those not expressing EpCAM, as analyzed using flow cytometry and confocal microscopy. The binding affinity of the EpCAM RNA aptamer to human cancer cells is approximately 55 nM. Importantly, this EpCAM RNA aptamer is efficiently internalized after binding to cell surface EpCAM. To our knowledge, this is the first RNA aptamer against a cancer stem cell surface marker being developed. Such cancer stem cell aptamers will greatly facilitate the development of novel targeted nanomedicine and molecular imaging agents for cancer theranostics.
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Shigdar
authors.forename: Jia
authors.initials: J
authors.lastname: Lin
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Mile
authors.initials: M
authors.lastname: Pastuovic
authors.forename: Ming
authors.initials: M
authors.lastname: Wei
authors.forename: Wei
authors.initials: W
authors.lastname: Duan
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002469:Cell Separation; D000071858:Epithelial Cell Adhesion Molecule; D005434:Flow Cytometry; D006801:Humans; D018613:Microscopy, Confocal; D014411:Neoplastic Stem Cells / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D052157:Aptamers, Nucleotide; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule