PMID- 28396463
OWN - NLM
STAT- MEDLINE
DCOM- 20180402
LR  - 20181113
IS  - 1557-3125 (Electronic)
IS  - 1541-7786 (Print)
IS  - 1541-7786 (Linking)
VI  - 15
IP  - 7
DP  - 2017 Jul
TI  - Blind SELEX Approach Identifies RNA Aptamers That Regulate EMT and Inhibit 
      Metastasis.
PG  - 811-820
LID - 10.1158/1541-7786.MCR-16-0462 [doi]
AB  - Identifying targets that are exposed on the plasma membrane of tumor cells, but 
      expressed internally in normal cells, is a fundamental issue for improving the 
      specificity and efficacy of anticancer therpeutics. Using blind cell Systemic 
      Evolution of Ligands by EXponetial enrichment (SELEX), which is untargeted SELEX, 
      we have identified an aptamer, P15, which specifically bound to the human 
      pancreatic adenocarcinoma cells. To identify the aptamer binding plasma membrane 
      protein, liquid chromatography tandem mass spectrometry (LC-MS/MS) was used. The 
      results of this unbiased proteomic mass spectrometry approach identified the 
      target of P15 as the intermediate filament vimentin, biomarker of 
      epithelial-mesenchymal transition (EMT), which is an intracellular protein but is 
      specifically expressed on the plasma membrane of cancer cells. As EMT plays a 
      pivotal role to transit cancer cells to invasive cells, tumor cell metastasis 
      assays were performed in vitro P15-treated pancreatic cancer cells showed the 
      significant inhibition of tumor metastasis. To investigate the downstream effects 
      of P15, EMT-related gene expression analysis was performed to identify 
      differently expressed genes (DEG). Among five DEGs, P15-treated cells showed the 
      downregulated expression of matrix metallopeptidase 3 (MMP3), which is involved 
      in cancer invasion. These results, for the first time, demonstrate that P15 
      binding to cell surface vimentin inhibits the tumor cell invasion and is 
      associated with reduced MMP3 expression. Thus, suggesting that P15 has potential 
      as an anti-metastatic therapy in pancreatic cancer.Implications: This study 
      reveals that anti-vimentin RNA aptamers selected via blind-SELEX inhibit the 
      tumor cell metastasis. Mol Cancer Res; 15(7); 811-20. (c)2017 AACR.
CI  - (c)2017 American Association for Cancer Research.
FAU - Yoon, Sorah
AU  - Yoon S
AD  - Department of Molecular and Cellular Biology, Beckman Research Institute of City 
      of Hope, Duarte, California.
FAU - Armstrong, Brian
AU  - Armstrong B
AD  - Light Microscopy Core, City of Hope, Duarte, California.
FAU - Habib, Nagy
AU  - Habib N
AD  - Department of Surgery and Cancer, Imperial College London, London, United 
      Kingdom.
FAU - Rossi, John J
AU  - Rossi JJ
AD  - Department of Molecular and Cellular Biology, Beckman Research Institute of City 
      of Hope, Duarte, California. jrossi@coh.org.
AD  - Irell and Manella Graduate School of Biological Sciences, Beckman Research 
      Institute of City of Hope, Duarte, California.
LA  - eng
GR  - P30 CA033572/CA/NCI NIH HHS/United States
GR  - R01 AI029329/AI/NIAID NIH HHS/United States
GR  - R01 AI042552/AI/NIAID NIH HHS/United States
GR  - R01 HL074704/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20170410
PL  - United States
TA  - Mol Cancer Res
JT  - Molecular cancer research : MCR
JID - 101150042
RN  - 0 (Aptamers, Nucleotide)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Ligands)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Adenocarcinoma/*genetics/pathology
MH  - Aptamers, Nucleotide/*administration & dosage/genetics
MH  - Biomarkers, Tumor/*genetics
MH  - Cell Line, Tumor
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Ligands
MH  - Matrix Metalloproteinase 3/*genetics
MH  - Neoplasm Invasiveness/genetics/pathology
MH  - Neoplasm Metastasis
MH  - Pancreatic Neoplasms/*genetics/pathology
MH  - Proteomics
MH  - SELEX Aptamer Technique
PMC - PMC5555160
MID - NIHMS867759
COIS- Disclosure of Potential Conflict of Interest: S.Y., N.H., and J.J.R. hold stocks 
      in Apterna Ltd. U.K.
EDAT- 2017/04/12 06:00
MHDA- 2018/04/03 06:00
PMCR- 2018/07/01
CRDT- 2017/04/12 06:00
PHST- 2016/12/13 00:00 [received]
PHST- 2017/01/17 00:00 [revised]
PHST- 2017/04/04 00:00 [accepted]
PHST- 2017/04/12 06:00 [pubmed]
PHST- 2018/04/03 06:00 [medline]
PHST- 2017/04/12 06:00 [entrez]
PHST- 2018/07/01 00:00 [pmc-release]
AID - 1541-7786.MCR-16-0462 [pii]
AID - 10.1158/1541-7786.MCR-16-0462 [doi]
PST - ppublish
SO  - Mol Cancer Res. 2017 Jul;15(7):811-820. doi: 10.1158/1541-7786.MCR-16-0462. Epub 
      2017 Apr 10.