Permissive State of EMT: The Role of Immune Cell Compartment.

Abstract

The Epithelial to Mesenchymal Transition (EMT) type 3 is a reversible dynamic process recognized as a major determinant of the metastatic event, although many questions regarding its role throughout this process remain unanswered. The ability of cancer cells to migrate and colonize distant organs is a key aspect of tumor progression and evolution, requiring constant tumor cells and tumor microenvironment (TME) changes, as well as constant changes affecting the cross-talk between the two aforementioned compartments. Alterations affecting tumor cells, such as transcription factors, trans-membrane receptors, chromatin remodeling complexes and metabolic pathways, leading to the disappearance of the epithelial phenotype and concomitant gaining of the undifferentiated mesenchymal phenotype are undoubtedly major players of the EMT process. However, several lines of evidence point out toward a more critical role of TME composition in creating an “EMT-permissive state.” The “EMT-permissive state” consists in changes affecting physical and biochemical properties (i.e., stiffness and/or hypoxia) as well as changes of the TME cellular component (i.e., immune-cell, blood vessel, lymphatic vessels, fibroblasts, and fat cells) that favor and induce the epithelial mesenchymal transition. In this mini review, we will discuss the role of the tumor microenvironment cellular component that are involved in supporting the EMT, with particular emphasis on the immune-inflammatory cells component.