RNA aptamer against a cancer stem cell marker epithelial cell adhesion molecule

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...

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Bibliographic Details
Published in:Cancer science 2011-05, Vol.102 (5), p.991-998
Main Authors: Shigdar, Sarah, Lin, Jia, Yu, Yan, Pastuovic, Mile, Wei, Ming, Duan, Wei
Format: Article
Language:English
Subjects:
Antigens, Neoplasm - metabolism
Aptamers
Aptamers, Nucleotide - chemistry
Aptamers, Nucleotide - metabolism
Biological and medical sciences
Cell adhesion molecules
Cell Adhesion Molecules - metabolism
Cell Separation
Cell surface
Chemotherapy
Confocal microscopy
Cytotoxicity
Epithelial Cell Adhesion Molecule
Epithelial cells
Evolution
Flow Cytometry
Gastric cancer
Humans
imaging
Medical sciences
Microscopy, Confocal
nanotechnology
Neoplastic Stem Cells - metabolism
Oligonucleotides
Stem cells
Surface markers
Tumors
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Summary: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. (Cancer Sci 2011; 102: 991–998)
ISSN:1347-9032
1349-7006
DOI:10.1111/j.1349-7006.2011.01897.x