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

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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.