Patel Nirmita, Baranwal Somesh, Patel Bhaumik B
Hunter Holmes McGuire VA Medical Center, 980230, Richmond, VA, 23249, USA.
Methods Mol Biol. 2015;1229:529-41. doi: 10.1007/978-1-4939-1714-3_41.
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（CSC）与传统化疗耐药以及侵袭和转移有关，导致包括结直肠癌在内的大多数上皮癌出现肿瘤复发。因此，通过小分子靶向CSC可能会改善治疗效果。糖胺聚糖（GAG）是具有不同硫酸化程度的长线性多糖分子，其允许特定的GAG-蛋白质相互作用，这在调节癌症特征（如细胞生长、血管生成和免疫调节）中起关键作用。然而，由于在体外分离和富集CSC存在困难，鉴定选择性靶向CSC的GAG模拟物一直受到阻碍。在此，我们讨论两种不同的方法，即球体生长和上皮-间质转化（EMT）细胞，以富集CSC，并建立中高通量筛选以鉴定选择性靶向CSC的药物。
