Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA.
Division of Hematology and Oncology, Department of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Methods Mol Biol. 2022;2303:765-777. doi: 10.1007/978-1-0716-1398-6_57.
Cancer stem-like cells (CSC) have been implicated in resistance to conventional chemotherapy as well as invasion and metastasis resulting in tumor relapse in majority of epithelial cancers including colorectal cancer. Hence, targeting CSC by small molecules is likely to improve therapeutic outcomes. Glycosaminoglycans (GAGs) are long linear polysaccharide molecules with varying degrees of sulfation that allows specific GAG-protein interaction which plays a key role in regulating cancer hallmarks such as cellular growth, angiogenesis, and immune modulation. However, identifying selective CSC-targeting GAG mimetic has been marred by difficulties associated with isolating and enriching CSC in vitro. Herein, we discuss two distinct methods, spheroid growth and EMT-transformed cells, to enrich CSC and set up medium- and high-throughput screen to identify selective CSC-targeting agents.
癌症干细胞样细胞 (CSC) 被认为与大多数上皮癌（包括结直肠癌）的常规化疗耐药性、侵袭和转移以及肿瘤复发有关。因此，通过小分子靶向 CSC 可能会改善治疗效果。糖胺聚糖 (GAG) 是具有不同程度硫酸化的长线性多糖分子，允许特定的 GAG-蛋白相互作用，在调节癌症特征（如细胞生长、血管生成和免疫调节）中发挥关键作用。然而，识别选择性 CSC 靶向 GAG 模拟物一直受到在体外分离和富集 CSC 相关困难的困扰。在此，我们讨论了两种不同的方法，球体生长和 EMT 转化细胞，来富集 CSC，并建立中高通量筛选以鉴定选择性 CSC 靶向药物。
