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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity
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Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity

机译：结肠癌干细胞的单细胞克隆揭示了多系分化能力

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摘要

Colon carcinoma is one of the leading causes of death from cancer and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, it was reported that a population of undifferentiated cells from a primary tumor, so-called cancer-stem cells (CSC), can reconstitute the original tumor on xenotransplantation. Here, we show that spheroid cultures of these colon CSCs contain expression of CD133, CD166, CD44, CD29, CD24, Lgr5, and nuclear β-catenin, which have all been suggested to mark the (cancer) stem cell population. More importantly, by using these spheroid cultures or freshly isolated tumor cells from multiple colon carcinomas, we now provide compelling evidence to indicate that the capacity to propagate a tumor with all differentiated progeny resides in a single CSC. Single-cell-cloned CSCs can form an adenocarcinoma on xenotransplantation but do not generate the stroma within these tumors. Moreover, they can self-renew and are capable of multilineage differentiation. Further analysis indicated that the lineage decision is dictated by phos-phoinositide 3-kinase (PI3K) signaling in CSCs. These data support the hypothesis that tumor hierarchy can be traced back to a single CSC that contains multilineage differentiation capacity, and provides clues to the regulation of differentiation in colon cancers in vivo.
机译：结肠癌是癌症死亡的主要原因之一，其特征是具有不同分化模式的细胞异质性池。最近，据报道，来自原发性肿瘤的未分化细胞群，即所谓的癌干细胞（CSC），可以在异种移植后重建原始肿瘤。在这里，我们显示这些结肠CSC的球状培养物包含CD133，CD166，CD44，CD29，CD24，Lgr5和核β-连环蛋白的表达，这些都被认为可以标记（癌症）干细胞群体。更重要的是，通过使用这些球状培养物或来自多个结肠癌的新鲜分离的肿瘤细胞，我们现在提供令人信服的证据表明，具有所有分化后代的肿瘤扩散能力都位于单个CSC中。单细胞克隆的CSC可以在异种移植时形成腺癌，但不会在这些肿瘤中产生基质。而且，它们可以自我更新，并且能够进行多系分化。进一步的分析表明，谱系决定是由CSC中的磷-磷酸肌醇3激酶（PI3K）信号决定的。这些数据支持这样的假设，即肿瘤的层次可以追溯到包含多谱系分化能力的单个CSC，并为体内结肠癌的分化调控提供线索。

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