School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
Cancer Sci. 2011 May;102(5):991-8. doi: 10.1111/j.1349-7006.2011.01897.x. Epub 2011 Mar 14.
The lack of a specific targeting strategy against cancer stem cells in current cancer treatment regimens is at least partly responsible for life-threatening cytotoxicity for patients undergoing traditional chemotherapy. An effective cancer stem cell targeting system is urgently required for the next generation of cancer medicine. Epithelial cell adhesion molecule (EpCAM) is overexpressed in most solid cancers and it has recently been identified as a cancer stem cell marker. In this study, we isolated a 40-base RNA aptamer that binds to EpCAM from a random oligonucleotide library using systematic evolution of ligands by exponential enrichment. The aptamer was further truncated to 19 bases. This 19-nt RNA aptamer interacts specifically with a number of live human cancer cells derived from breast, colorectal, and gastric cancers that express EpCAM, but not with those not expressing EpCAM, as analyzed using flow cytometry and confocal microscopy. The binding affinity of the EpCAM RNA aptamer to human cancer cells is approximately 55 nM. Importantly, this EpCAM RNA aptamer is efficiently internalized after binding to cell surface EpCAM. To our knowledge, this is the first RNA aptamer against a cancer stem cell surface marker being developed. Such cancer stem cell aptamers will greatly facilitate the development of novel targeted nanomedicine and molecular imaging agents for cancer theranostics.
当前癌症治疗方案缺乏针对癌症干细胞的特定靶向策略，这至少部分导致了接受传统化疗的患者发生危及生命的细胞毒性。下一代癌症药物迫切需要有效的癌症干细胞靶向系统。上皮细胞黏附分子（EpCAM）在大多数实体瘤中过度表达，最近被鉴定为癌症干细胞标志物。在这项研究中，我们使用指数富集的配体系统进化从随机寡核苷酸文库中分离出与 EpCAM 结合的 40 个碱基 RNA 适体。该适体进一步被截断为 19 个碱基。该 19 个碱基 RNA 适体与人乳腺癌、结直肠癌和胃癌来源的许多表达 EpCAM 的活癌细胞特异性相互作用，但与不表达 EpCAM 的细胞不相互作用，如流式细胞术和共聚焦显微镜分析所示。EpCAM RNA 适体与人癌细胞的结合亲和力约为 55 nM。重要的是，这种 EpCAM RNA 适体在与细胞表面 EpCAM 结合后能够有效内化。据我们所知，这是第一个针对癌症干细胞表面标志物的 RNA 适体。此类癌症干细胞适体将极大地促进新型靶向纳米医学和癌症治疗诊断的分子成像剂的开发。
