Cancer stem cells maintain a hierarchy of differentiation by creating their niche

摘要

The self-renewal and differentiation properties of cancer stem cells (CSCs) are regulated and maintained by the CSC niche. However, the mechanism of this maintenance, especially the maintenance contributed by differentiated cancer cells, remains to be fully elucidated. Recently, we have established a model of CSCs, miPS-LLCcm, from mouse induced pluripotent stem cells (miPSCs). In vitro cultured miPS-LLCcm cells were autonomously balanced with stem-like cells and differentiated cells including vascular endothelial cells. Under these conditions, the CSC properties appeared to be stable in the presence of the factor(s) secreted by the differentiated cells. The factor(s) activated Notch signaling and promoted self-renewal of CSCs. In addition, the secreted factor(s) appeared to regulate the differentiation lineage of CSCs. Our results indicate that the differentiated progenies of CSCs containing vascular endothelium play important roles for regulating the CSC's properties. Therefore, miPS-LLCcm cells create their own in vitro niche to maintain themselves in the hierarchy of differentiating CSCs. What's new? Cancer stem cells wreak their devastation by taking root in a supportive microenvironment that provides needed factors for both self-renewal and differentiation. But how does the microenvironment, or niche, sustain the stem cells? To investigate, these authors established a CSC system in vitro and assessed whether the progeny cells of CSCs need to stay nearby to create the stem cell niche. They found that the differentiated progeny cells do release factors that maintain the balance between self-renewal and differentiation in the stem cells, in part through the Notch signaling pathway. Understanding this dynamic will help researchers develop strategies to hinder cancer stem cells' ability to take hold.