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

在这项研究中，我们研究了癌症干细胞（CSC）在选择压力下的富集机制以及CSC逃避这种压力的方式。流式细胞术分析显示，透明质酸合成酶2 （Has2）过表达的癌细胞中，csc样细胞富集。我们还发现，过表达Has2的细胞产生的tnf - α和tgf - β水平明显高于对照细胞。综上所述，我们的发现提供了一种新颖的想法，即CSCs可以通过透明质酸依赖方式上调tnf - α诱导巨噬细胞激活，从而产生选择性压力。我们进一步认为，tgf - β的抗肿瘤免疫作用允许癌细胞逃避选择压力。

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.