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The DNA aptamer binds stemness-enriched cancer cells in pancreatic cancer

Authors
 Yoon-Jin Kim  ;  Hee Seung Lee  ;  Dawoon E. Jung  ;  Jeong Mi Kim  ;  Si Young Song 
Citation
 JOURNAL OF MOLECULAR RECOGNITION, Vol.30(4) : 2591, 2017 
Journal Title
 JOURNAL OF MOLECULAR RECOGNITION 
ISSN
 0952-3499 
Issue Date
2017
MeSH
AC133 Antigen/metabolism ; Aptamers, Nucleotide/chemistry ; Aptamers, Nucleotide/metabolism* ; Biomarkers, Tumor/metabolism ; CD24 Antigen/metabolism ; Cell Line, Tumor ; Humans ; Hyaluronan Receptors/metabolism ; Neoplastic Stem Cells/metabolism* ; Pancreatic Neoplasms/metabolism* ; SELEX Aptamer Technique
Keywords
aptamer ; cancer stem cell ; circulating tumor cell ; pancreatic cancer
Abstract
Pancreatic cancer remains one of the most common and lethal cancers. Most patients (80%) present with inoperable advanced pancreatic cancer at initial diagnosis, and their early diagnosis is a significant unmet challenge. Recent studies indicate that cancer, including pancreatic cancer, is initiated and propagated by cancer stem cells (CSCs). CSCs are responsible not only for the pathogenesis of cancer but also for the heterogeneity, malignant degree, anticancer therapy resistance, and recurrence of tumors. Therefore, the identification of CSCs may be a crucial stepping stone for overcoming this disastrous pancreatic cancer. Here, we investigated pancreatic CSC-associated aptamers as a novel tool for diagnosis and therapeutic agents. Aptamers that bind to stemness-enriched cancer cells in pancreatic cancer were developed by modified Cell-SELEX method. Positive selection was performed by the sphere cells generated by pancreatic cancer cell line, HPAC, and then the aptamer pool was negatively selected by pancreatic normal cell line, HPDE. Aptamers 1 and 146 showing high specificity upon the KD values with 22.18 and 22.62 nM were selected. These 2 aptamers were validated by binding to HPAC sphere cells and to HPDE cells, and both aptamers showed specificity to HPAC sphere cells only. Aptamer-positive cells showed high expression levels of CSC-associated genes compared with the aptamer-negative cells by FACS analysis. The colocalization of CD44, CD24, ESA, and CD133 was also observed in the aptamer-positive cells by confocal microscopy. In the present study, these 2 pancreatic CSC-associated aptamers may be potential candidates for novel diagnostic markers, CSC-targeting drug delivery, or circulating tumor cell detection.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/jmr.2591/abstract
DOI
10.1002/jmr.2591
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute of Gastroenterology (소화기병연구소) > 1. Journal Papers
Yonsei Authors
Kim, Jeong Mi(김정미)
Song, Si Young(송시영) ORCID logo https://orcid.org/0000-0002-1417-4314
Lee, Hee Seung(이희승) ORCID logo https://orcid.org/0000-0002-2825-3160
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154553
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