Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4
Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4
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DOI：
10.1016/j.stem.2007.08.001
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发表时间：
2007-10-01
期刊：
影响因子：
23.9
通讯作者：
Stassi, Giorgio
中科院分区：
文献类型：
--
作者：
Todaro, Matilde;Alea, Mileidys Perez;Stassi, Giorgio
肿瘤生物学中的一种新范式表明，肿瘤内的干细胞样细胞推动了癌症的生长。在这里，我们描述了使用干细胞标记物CD133从结肠癌中鉴定和鉴定这类细胞的方法，CD133约占人类结肠癌细胞的2%。CD133(+)细胞在体外以未分化的肿瘤球体的形式生长，它们是启动免疫缺陷小鼠肿瘤生长的必要条件和充分条件。异种移植类似于原始的人类肿瘤，保持了罕见的致瘤CD133(+)细胞亚群。进一步的分析表明，CD133(+)细胞产生并利用IL-4来保护自己免受凋亡。持续使用IL-4Rα拮抗剂或抗IL-4中和抗体可通过选择性敏化CD133(+)细胞来增强标准化疗药物的抗肿瘤效果。我们的数据表明，结肠肿瘤的生长是由干细胞样细胞决定的，由于IL-4的自分泌产生，干细胞对治疗具有抵抗力。
A novel paradigm in tumor biology suggests that cancer growth is driven by stem-like cells within a tumor. Here, we describe the identification and characterization of such cells from colon carcinomas using the stem cell marker CD133 that accounts around 2% of the cells in human colon cancer. The CD133(+) cells grow in vitro as undifferentiated tumor spheroids, and they are both necessary and sufficient to initiate tumor growth in immunodeficient mice. Xenografts resemble the original human tumor maintaining the rare subpopulation of tumorigenic CD133(+) cells. Further analysis revealed that the CD133(+) cells produce and utilize IL-4 to protect themselves from apoptosis. Consistently, treatment with IL-4R alpha antagonist or anti-IL-4 neutralizing antibody strongly enhances the antitumor efficacy of standard chemotherapeutic drugs through selective sensitization of CD133(+) cells. Our data suggest that colon tumor growth is dictated by stem-like cells that are treatment resistant due to the autocrine production of IL-4.