title: Blocking the attachment of cancer cells in vivo with DNA aptamers displaying anti-adhesive properties against the carcinoembryonic antigen.
abstract: The formation of metastatic foci occurs through a series of cellular events, initiated by the attachment and aggregation of cancer cells leading to the establishment of micrometastases. We report the derivation of synthetic DNA aptamers bearing anti-adhesive properties directed at cancer cells expressing the carcinoembryonic antigen (CEA). Two DNA aptamers targeting the homotypic and heterotypic IgV-like binding domain of CEA were shown to block the cell adhesion properties of CEA, while not recognizing other IgV-like domains of CEACAM family members that share strong sequence and structural homologies. More importantly, the pre-treatment of CEA-expressing tumour cells with these aptamers prior to their intraperitoneal implantation resulted in the prevention of peritoneal tumour foci formation. Taken together, these results highlight the effectiveness of targeting the cell adhesion properties of cancer cells with aptamers in preventing tumour implantation.
authors: Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors: Erik W
authors: EW
authors: Orava
authors: Aws
authors: A
authors: Abdul-Wahid
authors: Eric H-B
authors: EH
authors: Huang
authors: Amirul Islam
authors: AI
authors: Mallick
authors: Jean
authors: J
authors: Gariépy
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects; D051379:Mice; D008954:Models, Biological; D017433:Protein Structure, Secondary
chemical_list: D015703:Antigens, CD; D052157:Aptamers, Nucleotide; D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; C575659:Gm5893 protein, mouse
keywords: Adhesion; CEA; DNA aptamers; Homotypic binding; Metastatic cancer
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