Selective pressure driving cancer cell fate decisions: the mechanism of the creation

在这项研究中，我们研究了选择性压力下肿瘤干细胞(CSC)的浓缩机制，以及CSC如何逃脱这种压力。流式细胞仪分析显示高表达透明质酸合成酶2(Has2)的癌细胞中有CSC样细胞的聚集。我们还发现，Has2过表达细胞产生的肿瘤坏死因子-α和转化生长因子-β水平显著高于对照细胞。综上所述，我们的发现提供了一个新的想法，即CSCs可以通过以透明质酸依赖的方式上调肿瘤坏死因子-α诱导的巨噬细胞激活来产生选择性压力。我们进一步认为，转化生长因子-β的抗肿瘤免疫作用使癌细胞能够逃脱选择性压力。

In this study, we have investigated the mechanisms of cancer stem cell (CSC) enrichment under the selective pressure and the way in which CSCs can escape from this pressure. Flow cytometric analysis indicated the enrichment of CSC-like cells in hyaluronan synthase 2 (Has2)-overexpressing cancer cells. We also found that Has2 overexpressing cells produced significantly higher levels of TNF-alpha and TGF-beta than the control cells. Taken together, our findings provided a novel idea that CSCs can create selective pressure via the macrophage activation induced by up-regulating TNF-alpha in a hyaluronan-dependent manner. We further suggest that the anti-tumor immune action of TGF-beta allows cancer cells to escape from the selective pressure.