Esposito Carla Lucia, Quintavalle Cristina, Ingenito Francesco, Rotoli Deborah, Roscigno Giuseppina, Nuzzo Silvia, Thomas Renato, Catuogno Silvia, de Franciscis Vittorio, Condorelli Gerolama
Institute for Experimental Endocrinology and Oncology, "G.Salvatore" IEOS, Consiglio Nazionale delle Ricerche (CNR), 80131 Naples, Italy.
Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II," 80100 Naples, Italy.
Mol Ther Nucleic Acids. 2021 Jan 20;23:982-994. doi: 10.1016/j.omtn.2021.01.012. eCollection 2021 Mar 5.
Breast cancer is a leading cause of cancer mortality in women. Despite advances in its management, the identification of new options for early-stage diagnosis and therapy of this tumor still represents a crucial challenge. Increasing evidence indicates that extracellular vesicles called exosomes may have great potential as early diagnostic biomarkers and regulators of many cancers, including breast cancer. Therefore, exploiting molecules able to selectively recognize them is of great interest. Here, we developed a novel differential SELEX strategy, called Exo-SELEX, to isolate nucleic acid aptamers against intact exosomes derived from primary breast cancer cells. Among the obtained sequences, we optimized a high-affinity aptamer (ex-50.T) able to specifically recognize exosomes from breast cancer cells or patient serum samples. Furthermore, we demonstrated that the ex.50.T is a functional inhibitor of exosome cellular uptake and antagonizes cancer exosome-induced cell migration . This molecule provides an innovative tool for the specific exosome detection and the development of new therapeutic approaches for breast cancer.
乳腺癌是女性癌症死亡的主要原因。尽管其治疗取得了进展,但确定该肿瘤早期诊断和治疗的新方法仍然是一项关键挑战。越来越多的证据表明,称为外泌体的细胞外囊泡作为许多癌症(包括乳腺癌)的早期诊断生物标志物和调节剂可能具有巨大潜力。因此,开发能够选择性识别它们的分子具有重要意义。在这里,我们开发了一种名为Exo-SELEX的新型差异SELEX策略,以分离针对源自原发性乳腺癌细胞的完整外泌体的核酸适配体。在获得的序列中,我们优化了一种高亲和力适配体(ex-50.T),它能够特异性识别来自乳腺癌细胞或患者血清样本的外泌体。此外,我们证明ex.50.T是外泌体细胞摄取的功能抑制剂,并拮抗癌症外泌体诱导的细胞迁移。该分子为特异性外泌体检测和乳腺癌新治疗方法的开发提供了一种创新工具。