Abstract：
:Glioblastomas display cellular hierarchies with self-renewing tumor-initiating cells (TIC), also known as cancer stem cells, at the apex. Although the TIC hypothesis remains controversial and the functional assays to define the TIC phenotype are evolving, we and others have shown that TICs may contribute to therapeutic resistance, tumor spread, and angiogenesis. The identification of TICs has been informed by the use of markers characterized in normal stem cells, but this approach has an inherent limitation to selectively identify TICs. To develop reagents that enrich TICs but not matched non-TICs or tissue-specific stem cells, we adopted Cell-Systematic Evolution of Ligands by Exponential Enrichment (Cell-SELEX) to identify glioblastoma TIC-specific nucleic acid probes-aptamers-that specifically bind TICs. In this study, using Cell-SELEX with positive selection for TICs and negative selection for non-TICs and human neural progenitor cells, we identified TIC aptamers that specifically bind to TICs with excellent dissociation constants (Kd). These aptamers select and internalize into glioblastoma cells that self-renew, proliferate, and initiate tumors. As aptamers can be modified to deliver payloads, aptamers may represent novel agents that could selectively target or facilitate imaging of TICs.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Kim Y,Wu Q,Hamerlik P,Hitomi M,Sloan AE,Barnett GH,Weil RJ,Leahy P,Hjelmeland AB,Rich JNdoi
10.1158/0008-5472.CAN-12-4556subject
Has Abstractpub_date
2013-08-01 00:00:00pages
4923-36issue
15eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-12-4556journal_volume
73pub_type
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