在原发性和转移性结肠癌中Lgr5+干细胞的独特作用
Felipe de Sousa e Melo1, Antonina V Kurtova1, Jonathan M Harnoss2
1Molecular Oncology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA.
Nature
|March 31, 2017
概括
癌症干细胞驱动瘤的生长和转移. 向Lgr5+CSC可以抑制原发性瘤,但不能治愈它们,因为Lgr5-细胞可以补偿,突出显示原发性与转移性结肠直肠癌中的不同CSC作用.
科学领域:
- 癌症学
- 胃肠病学
- 细胞生物学
背景情况:
- 癌症干细胞 (CSC) 参与瘤的进展和转移.
- 它们对大多数癌症的功能相关性在实验上尚未得到证实.
- 确定特定的CSC标记对于向癌症治疗至关重要.
研究的目的:
- 研究含有丰富的白蛋白重复结合受体5 (Lgr5) 在识别和向肠癌干细胞 (CSC) 中的作用.
- 确定Lgr5+ CSCs在原发性瘤生长和结直肠癌转移中的功能相关性.
- 探索针对CSC治疗转移性疾病的治疗策略.
主要方法:
- 复制人类结直肠癌进展的工程小鼠模型.
- 选择性切除Lgr5表达细胞 (Lgr5+).
- 对原发性瘤生长,回归和转移潜力的分析.
主要成果:
- 在工程结直肠癌模型中,Lgr5识别了肠道CSC.
- 选择性Lgr5+细胞切除限制了原发性瘤的生长,但没有导致回归.
- 在停止治疗后,Lgr5- 细胞补充了Lgr5+ CSC池,导致瘤再生.
- 对于肝转移的形成和维持,CSCs具有关键作用.
结论:
- 对于原发性与转移性瘤生长存在明显的CSC依赖性.
- 向Lgr5+CSC可能是治疗转移性结直肠癌的策略.
- 可以补偿Lgr5+CSC的损失,这表明可能需要组合治疗.
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