Biomarkers for epithelial-mesenchymal transitions

Abstract

Somatic cells that change from one mature phenotype to another exhibit the property of plasticity. It is increasingly clear that epithelial and endothelial cells enjoy some of this plasticity, which is easily demonstrated by studying the process of epithelial-mesenchymal transition (EMT). Published reports from the literature typically rely on ad hoc criteria for determining EMT events; consequently, there is some uncertainty as to whether the same process occurs under different experimental conditions. As we discuss in this Personal Perspective, we believe that context and various changes in plasticity biomarkers can help identify at least three types of EMT and that using a collection of criteria for EMT increases the likelihood that everyone is studying the same phenomenon - namely, the transition of epithelial and endothelial cells to a motile phenotype.

Figure 1. Epithelial cell plasticity can be viewed as a form of either transdifferentiation (metaplasia) or EMT.

Transdifferentiation generally refers to a process whereby one mature epithelial cell phenotype converts into a different mature epithelial cell, with or without cell division. It is unclear whether transdifferentiation involves a transition state. Three types of EMT are recognized depending on the phenotype of the output cells. Type 1 EMT is seen when primitive epithelial cells transition into mesenchymal cells that form the diaspora of the basic body plan following gastrulation or neural crest migration. These mesenchymal cells either undergo MET to form secondary epithelial cells or apoptose. Type 2 EMT is seen when secondary epithelial cells or endothelial cells populate interstitial spaces with resident or inflammation-induced fibroblasts, the latter during persistent injury. Type 3 EMT is part of the metastatic process, whereby epithelial tumor cells leave a primary tumor nodule, migrate to a new tissue site, and reform as a secondary tumor nodule.