A strategic approach to identification of selective inhibitors of cancer stem cells.
A strategic approach to identification of selective inhibitors of cancer stem cells.
复制标题
鉴定癌症干细胞选择性抑制剂的战略方法。
DOI：
10.1007/978-1-4939-1714-3_41
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Patel,BhaumikB
中科院分区：
文献类型：
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作者：
Patel,Nirmita;Baranwal,Somesh;Patel,BhaumikB
癌症干细胞样细胞（CSC）与传统化疗的耐药性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的肿瘤复发。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，可实现特定的 GAG-蛋白质相互作用，在调节细胞生长、血管生成和免疫调节等癌症标志中发挥关键作用。然而，选择性 CSC 靶向 GAG 模拟物的鉴定因体外分离和富集 CSC 相关的困难而受到损害。在此，我们讨论了两种不同的方法，即球体生长和 EMT 转化细胞，以富集 CSC 并建立中和高通量筛选来识别选择性 CSC 靶向剂。
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.