Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada.
Mol Oncol. 2013 Aug;7(4):799-811. doi: 10.1016/j.molonc.2013.03.005. Epub 2013 Apr 11.
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.
转移灶的形成是通过一系列细胞事件发生的,这些事件由癌细胞的附着和聚集引发,导致微转移的建立。我们报告了具有抗黏附特性的合成 DNA 适体的衍生,这些适体针对表达癌胚抗原(CEA)的癌细胞。两种针对 CEA 同种型和异型 IgV 样结合域的 DNA 适体被证明可以阻断 CEA 的细胞黏附特性,而不识别 CEACAM 家族成员的其他具有强序列和结构同源性的 IgV 样结构域。更重要的是,在将表达 CEA 的肿瘤细胞腹膜内植入之前,用这些适体对其进行预处理,可防止腹膜肿瘤灶的形成。总之,这些结果突出了用适体靶向癌细胞的黏附特性来预防肿瘤植入的有效性。