title: An RNA aptamer that binds carcinoembryonic antigen inhibits hepatic metastasis of colon cancer cells in mice.
abstract: OBJECTIVE
  Carcinoembryonic antigen (CEA) is expressed by many types of cancer cells; its overexpression induces cell adhesion, increases resistance to anoikis, and promotes hepatic metastasis of colon cancer cells. The amino acid sequence PELPK in its hinge region, between the N and A1 domains, is required for migration of cancer cells to the liver. We sought to identify ligands of this domain for use in diagnosis and therapy.
  
  
  METHODS
  We screened for RNA aptamers against the domain of CEA required for metastasis using systematic evolution of ligands by exponential enrichment. The specificity and affinity of the aptamer for CEA protein were characterized by mobility shift, uptake, and surface plasmon resonance assays. We analyzed the effects of the aptamer on metastatic properties of cells, as well as metastasis of colon cancer cells in mice.
  
  
  RESULTS
  Using systematic evolution of ligands by exponential enrichment, we identified an RNA aptamer that bound to the PELPK sequence in CEA with high affinity and specificity. The isolated aptamer bound specifically to CEA-positive cells and inhibited interactions between CEA and heterogeneous nuclear ribonucleoprotein M4. The aptamer inhibited homotypic aggregation, migration, and invasion by CEA-positive cancer cells, but did not affect adhesion of endothelial cells. The aptamer induced colon cancer cell anoikis by interrupting the interaction between death receptor 5 and CEA. The aptamer prevented metastasis of human colon cancer cells to the livers of mice.
  
  
  CONCLUSIONS
  An RNA aptamer that binds to the PELPK sequence in CEA inhibits its interactions with heterogeneous nuclear ribonucleoprotein M4 and death receptor 5, migration and invasion by colon cancer cells, and hepatic metastasis of colon cancer cells in mice. It promoted cancer cell anoikis and might be used to identify CEA-positive tumors in patients or be developed as an anti-cancer reagent.
authors.affiliation: Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Yongin, Republic of Korea.
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Lee
authors.forename: Seung Ryul
authors.initials: SR
authors.lastname: Han
authors.forename: Nam Yeon
authors.initials: NY
authors.lastname: Kim
authors.forename: Soo-Han
authors.initials: SH
authors.lastname: Lee
authors.forename: Jin-Sook
authors.initials: JS
authors.lastname: Jeong
authors.forename: Seong-Wook
authors.initials: SW
authors.lastname: Lee
mesh_terms: D000818:Animals; D023102:Anoikis / Q000187:drug effects; D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D008099:Liver / Q000187:drug effects*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D051379:Mice
chemical_list: D052157:Aptamers, Nucleotide; D002272:Carcinoembryonic Antigen