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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion
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Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion

机译：乳腺癌干细胞的诱导形成及其通过IL6分泌与非干细胞的动态平衡

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摘要

Tumors are often heterogeneous, being composed of multiple cell types with different phenotypic and molecular properties. Cancer stem-like cells (CSCs) are a highly tumorigenic cell type found in developmentally diverse tumors or cancer cell lines, and they are often resistant to standard chemotherapeutic drugs. The origins of . CSCs and their relationships to nonstem cancer cells (NSCCs) are poorly understood. In an inducible breast oncogenesis model, CSCs are generated from nontransformed cells at a specific time during the transformation process, but CSC formation is not required for transformation. MicroRNA profiles indicate that CSCs and NSCCs are related, but different cell types arising from a common non-transformed population. Interestingly, medium from the transformed population stimulates NSCCs to become CSCs, and conversion of NSCCs to CSCs occurs in mouse xenografts. fuerthermore, IL6 is sufficient to convert NSCCs to CSCs in genetically different breast cell lines, human breast tumors, and a prostate cell line. Thus, breast and prostate CSCs and NSCCs do not represent distinct epigenetic states, and these CSCs do not behave as or arise from classic stem cells. Instead, tumor heterogeneity involves a dynamic equilibrium between CSCs and NSCCs mediated by IL6 and activation of the inflammatory feedback loop required for oncogenesis. This dynamic equilibrium provides an additional rationale for combining conventional chemotherapy with metformin, which selectively inhibits CSCs.
机译：肿瘤通常是异质的，由具有不同表型和分子特性的多种细胞类型组成。癌症干细胞样细胞（CSC）是在多种多样的肿瘤或癌细胞系中发现的高度致瘤细胞类型，它们通常对标准化学治疗药物具有抗性。的起源。人们对CSC及其与非干癌细胞（NSCC）的关系了解甚少。在可诱导的乳房癌发生模型中，CSC是在转化过程中的特定时间从未转化的细胞生成的，但是转化不需要CSC的形成。 MicroRNA谱表明CSC和NSCC是相关的，但不同的细胞类型是由共同的非转化群体引起的。有趣的是，来自转化种群的培养基刺激NSCC成为CSC，并且在小鼠异种移植物中发生了NSCC向CSC的转化。此外，IL6足以在遗传上不同的乳腺细胞系，人乳腺肿瘤和前列腺细胞系中将NSCCs转换为CSC。因此，乳房和前列腺CSC和NSCC不代表不同的表观遗传状态，并且这些CSC不表现为经典干细胞或源自经典干细胞。相反，肿瘤异质性涉及由IL6介导的CSC与NSCC之间的动态平衡，以及肿瘤发生所需的炎症反馈回路的激活。这种动态平衡为常规化疗与二甲双胍联合使用提供了额外的理由，二甲双胍可选择性抑制CSC。

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