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首页> 外文期刊>Cell cycle >Human colon cancer stem cells are enriched by insulin-like growth factor-1 and are sensitive to figitumumab.
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Human colon cancer stem cells are enriched by insulin-like growth factor-1 and are sensitive to figitumumab.

机译：人结肠癌干细胞富含胰岛素样生长因子-1，并且对figitumumab敏感。

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Cancer stem cells (CSCs) are recognized as contributors to cancer progression and therapeutic resistance in liquid and solid malignancies. We analyzed a panel of human colon cancer cell lines for CSC populations by side population and aldehyde dehydrogenase activity. IGF-1 enriches these putative colon CSC populations in a beta-catenin-dependent manner. Chemical inhibition of Akt depletes SP cells, and conversely, the overexpression of a constitutively active mutant version of Akt is sufficient to enrich CSC populations. CP-751,871, a fully human antibody with specificity to the IGF-1 receptor, is currently being tested in clinical trials for a variety of solid tumors. CP-751,871 reduces CSC populations in colon cancer cell lines in vitro and reduces tumor growth in vivo. We have identified a novel role for IGF-1 in the enrichment of chemo-resistant CSC populations. Our results suggest that CP-751,871 has preferential activity against putative CSC populations and, therefore, may complement current standard chemotherapeutic regimens that target cycling cells.
机译：癌症干细胞（CSC）被认为是液体和固体恶性肿瘤中癌症进展和治疗抗性的贡献者。我们通过侧群和醛脱氢酶活性分析了人类结肠癌细胞系的CSC群体。 IGF-1以β-catenin依赖的方式丰富了这些假定的结肠CSC群体。 Akt的化学抑制作用会耗尽SP细胞，相反，Akt的组成型活性突变体版本的过表达足以富集CSC种群。 CP-751,871是对IGF-1受体具有特异性的完全人类抗体，目前正在临床试验中针对多种实体瘤进行测试。 CP-751,871可在体外减少结肠癌细胞系中的CSC种群，并在体内减少肿瘤的生长。我们已经确定了IGF-1在抗化学性CSC人群中的新作用。我们的结果表明，CP-751,871对假定的CSC群体具有优先活性，因此，可以补充目前针对循环细胞的标准化学治疗方案。

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