Chen Luxi, Long Chao, Tran Kha Andy Minh, Lee Jiyong
Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 W. Campbell Rd., Richardson, TX, 75080, USA.
Chemistry. 2018 Mar 12;24(15):3694-3698. doi: 10.1002/chem.201705663. Epub 2018 Feb 19.
Cancer stem cells (CSCs) are associated with drug resistance, metastasis and recurrence of cancer. A synthetic binder of CSCs can provide a valuable tool to study the biology of CSCs and a lead to develop imaging, diagnostic and therapeutic agents targeting CSCs. Herein, a synthetic ligand (1) that specifically binds to CSCs over non-CSCs of breast cancer cells was identified for the first time via a cell-binding screening of a chemical library. The ligand 1 showed specific binding to CD24 /CD44 /ALDH CSC population of MCF-7 and MDA-MB-231. We have demonstrated that 1-immobilized beads can be used as matrices for affinity isolation of 1-binding CSC population from breast cancer cells. The 1-binding population showed significantly increased expressions of stemness-associated transcription factors. Importantly, the 1-binding population demonstrated accelerated tumor growth in vivo, and the resulting tumor displayed an increased migratory activity and high expressions of CSC markers.
癌症干细胞（CSCs）与癌症的耐药性、转移和复发相关。癌症干细胞的合成结合剂可为研究癌症干细胞生物学提供有价值的工具，并为开发靶向癌症干细胞的成像、诊断和治疗药物提供线索。在此，通过对化学文库进行细胞结合筛选，首次鉴定出一种合成配体（1），其对乳腺癌细胞的癌症干细胞具有特异性结合，而对非癌症干细胞无此特性。配体1显示出与MCF-7和MDA-MB-231的CD24/CD44/ALDH癌症干细胞群体特异性结合。我们已经证明，固定有1的珠子可作为从乳腺癌细胞中亲和分离与1结合的癌症干细胞群体的基质。与1结合的群体显示干性相关转录因子的表达显著增加。重要的是，与1结合的群体在体内表现出加速的肿瘤生长，并且所形成的肿瘤显示出增加的迁移活性和癌症干细胞标志物的高表达。
