Camorani Simona, Granata Ilaria, Collina Francesca, Leonetti Francesco, Cantile Monica, Botti Gerardo, Fedele Monica, Guarracino Mario Rosario, Cerchia Laura
Institute of Experimental Endocrinology and Oncology "G. Salvatore" (IEOS), National Research Council (CNR), Naples 80131, Italy.
Computational and Data Science Laboratory, High Performance Computing and Networking Institute, National Research Council (CNR), Naples 80131, Italy.
iScience. 2020 Apr 24;23(4):100979. doi: 10.1016/j.isci.2020.100979. Epub 2020 Mar 12.
Triple-negative breast cancer (TNBC) is a high heterogeneous group of tumors with a distinctly aggressive nature and high rates of relapse. So far, the lack of any known targetable proteins has not allowed a specific anti-tumor treatment. Therefore, the identification of novel agents for specific TNBC targeting and treatment is desperately needed. Here, by integrating cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) for the specific recognition of TNBC cells with high-throughput sequencing technology, we identified a panel of 2'-fluoropyrimidine-RNA aptamers binding to TNBC cells and their cisplatin- and doxorubicin-resistant derivatives at low nanomolar affinity. These aptamers distinguish TNBC cells from both non-malignant and non-TNBC breast cancer cells and are able to differentiate TNBC histological specimens. Importantly, they inhibit TNBC cell capacity of growing in vitro as mammospheres, indicating they could also act as anti-tumor agents. Therefore, our newly identified aptamers are a valuable tool for selectively dealing with TNBC.
三阴性乳腺癌（TNBC）是一组高度异质性的肿瘤，具有明显的侵袭性和高复发率。到目前为止，由于缺乏任何已知的可靶向蛋白，无法进行特异性抗肿瘤治疗。因此，迫切需要鉴定用于特异性靶向和治疗TNBC的新型药物。在此，通过将用于特异性识别TNBC细胞的细胞SELEX（指数富集的配体系统进化）与高通量测序技术相结合，我们鉴定出一组2'-氟嘧啶-RNA适配体，它们以低纳摩尔亲和力与TNBC细胞及其顺铂和阿霉素耐药衍生物结合。这些适配体能够区分TNBC细胞与非恶性和非TNBC乳腺癌细胞，并且能够区分TNBC组织标本。重要的是，它们抑制TNBC细胞在体外形成乳腺球生长的能力，表明它们也可以作为抗肿瘤药物。因此，我们新鉴定的适配体是选择性处理TNBC的有价值工具。
