Given my descriptions of epithelial to mesenchymal transition (EMT) in cancer progression, it seems appropriate to revisit the validity of it as a real phenomenon. David Tarin and Thompson & Newgreen engaged in a point-counterpoint review last year in Cancer Research on this very topic.
I would describe Tarin’s position is that of the clinical pathologist, rigorously defining cell lineages according to their expression profiles, functional phenotypes, and behaviors in vivo. Specifically, Tarin addresses two areas of suppposed support for EMT – possible EMT in embryonic development, and from extrapolated observations in vitro – before examining the lack of evidence for a true, stable conversion of one differentiated cell lineage into another at any cancer stage.
I’ll leave it to you to read the review for yourself, but to summarize here, Tarin says:
Histologic appearances which superficially seem to resemble the descriptions of EMT do sometimes occur in human tumors but do not withstand close scrutiny. Disorderly differentiation, loss of cell polarity and loss of lineage specific or tissue specific cytologic features are defining aspects of carcinomas.
The many biochemical and molecular biological investigations founded upon the hypothesis of EMT have produced substantial amounts of interesting data, but the fundamental premise that EMT occurs in real cancers is seriously in doubt and the interpretation of the molecular observations needs to be revisited. According to histopathologic criteria, these findings seem unlikely to be directly informative about the mechanisms underlying the dynamic progression of human and animal tumors in vivo, but may still provide information on the molecular options available to cancer cells in vitro. This story is a classic example of the need to incorporate histopathologic expertise on human and animal cancers into modern cancer research, in order to make basic mechanistic investigations relevant to the clinical management of neoplasia.
I’d say that’s a pretty fair summary, based upon my knowledge of the subject. However, I also agree that Tarin is parsing the terminology involved when describing the dysregulation of cellular morphology and adhesion in malignant transformation.
In the counterpoint, Erik Thompson and Donald Newgreen, present this view – that the gap between their differing perspectives may be largely semantics:
Exactly what constitutes an EMT is somewhat open to interpretation, and we have tended to be more inclusive than [Tarin].
In a sense, I think a number of cell biologists (myself included when I’m not careful) just inadvertantly overuse the term EMT, making it sound like a true transition in cellular differentiation. As Tarin says, it isn’t. I consider EMT as more of a loss of differentiation than a change in cell fate, hence the various terms available to describe the new mesenchymal-like phenotype: ameobiod, fibroblast-like, etc.
- The Fallacy of Epithelial Mesenchymal Transition in Neoplasia. Tarin D, Thompson EW, Newgreen DF. Cancer Res. 2005 Jul 15; 65(14):5996-6000; discussion 6000-1. Pubmed