Selection and characterization of DNA aptamer for metastatic prostate cancer recognition and tissue imaging.
Selection and characterization of DNA aptamer for metastatic prostate cancer recognition and tissue imaging.
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用于转移性前列腺癌识别和组织成像的 DNA 适体的选择和表征
DOI：
10.18632/oncotarget.9262
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发表时间：
2016-06-14
期刊：
影响因子：
--
通讯作者：
Tan W
中科院分区：
文献类型：
--
作者：
Duan M;Long Y;Yang C;Wu X;Sun Y;Li J;Hu X;Lin W;Han D;Zhao Y;Liu J;Ye M;Tan W
前列腺癌(PCa)是男性第二大死亡原因，也是最常见的癌症。缺乏抗去势转移性前列腺癌的治疗选择，以及能够区分惰性和侵袭性肿瘤的生物标记物，导致了这些统计数据。在本研究中，通过基于细胞的系统进化指数富集法(SELEX)，成功地筛选出了针对人前列腺癌DU145细胞的DNA适配子DML-7。所选择的适体DML-7被发现以依赖于温度的方式内化到靶细胞中，并与解离常数在纳摩尔范围内的靶细胞显示出高的结合亲和力。结合分析进一步表明，DML-7只与有转移潜能的DU145和PC-3细胞结合，而不与低转移潜能或非转移潜能的LNCaP或22Rv1细胞结合，表明DML-7对转移的PCa细胞具有良好的识别选择性。临床组织成像进一步证实了这些结果。因此，DML-7对转移性前列腺癌细胞和组织具有较高的亲和力和特异性，有望发展成为前列腺癌诊断和靶向给药的新工具。
Prostate cancer (PCa) is the second leading cause of death and most prevalent cancer in men. The absence of curative options for castration-resistant metastatic prostate cancer and biomarkers able to discriminate between indolent and aggressive tumors contribute to these statistics. In this study, a DNA aptamer termed DML-7 was successfully selected against human PCa cell line DU145 by using the cell-based systematic evolution of ligands by exponential enrichment (SELEX) method. The selected aptamer DML-7 was found to internalize into target cells in a temperature-dependent manner and exhibit high binding affinity for target cells with dissociation constants in the nanomolar range. Binding analysis further revealed that DML-7 only binds to DU145 and PC-3 cells with metastatic potential, but not to LNCaP or 22Rv1 cells with low or nonmetastatic potential, demonstrating that DML-7 has excellent selectivity for the recognition of the metastatic PCa cells. Clinical tissue imaging further confirmed these results. Therefore, both high binding affinity and specificity to metastatic PCa cells and tissues afford DML-7 with the potential for development into a novel tool for diagnosis and targeted drug delivery against metastatic prostate cancer.
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