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

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    Accepted Manuscript (AM)
    Author(s)
    Shigdar, Sarah
    Lin, Jia
    Yu, Yan
    Pastuovic, Mile
    Wei, Ming
    Duan, Wei
    Griffith University Author(s)
    Wei, Ming Q.
    Year published
    2011
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    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 ...
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    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.
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    Journal Title
    Cancer Science
    Volume
    102
    Issue
    5
    DOI
    https://doi.org/10.1111/j.1349-7006.2011.01897.x
    Copyright Statement
    © 2011 Japanese Cancer Association. This is the peer reviewed version of the following article: RNA aptamer against a cancer stem cell marker epithelial cell adhesion molecule, Cancer Science, Volume 102, Issue 5, Pages 991–998, 2011, which has been published in final form at 10.1111/j.1349-7006.2011.01897.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-20227.html#terms)
    Subject
    Oncology and carcinogenesis
    Cancer therapy (excl. chemotherapy and radiation therapy)
    Pharmacology and pharmaceutical sciences
    Publication URI
    http://hdl.handle.net/10072/41422
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