Nature Reviews Cancer has an opinion piece of interest to this blog by Carla Boccaccio and Paolo Comoglio: Invasive growth: a MET-driven genetic programme for cancer and stem cells. This is significant both in light of the epithelial to mesenchymal transition (EMT) and the stem cell theory of neoplasms, both of which I think appear to be popular but incorrect models of cancer progression.
Boccaccio and Comoglio argue that:
Althought perceived as a subversion of tissue structure and function, the process of invasion and metastasis probably originates from a physiological property of undifferentiated stem and/or progenitor cells.
They note, too, that neoplastic cells undergo (superficially) similar phenotypic changes, and frequently utilize molecular determinants of morphogenesis. And that’s correct – to a point.
What they leave out is the recognition that the phenotypic change is not a true change in the differentiation state to a new cell lineage, but is instead an acquired deprogramming towards dysregulation of the genetic program or the epigenetic regulation of this program.
How significant is this distinction? Admittedly, not very. Boccaccio and Comoglio’s characterization of the biochemical elements of cancer progression, involving MET, HGF, and other factors, is spot on. Yet, I’m skeptical of their call to “identify, characterize rare cancer stem cells,” as if a good strategy is to discover a hidden cell type that is programmed to initiate neoplasms. Instead, a much better strategy for oncological therapy would be to expand and catalog the wide array of possible (epi)genetic predispositions for generating cellular dysfunction, and characterize the potential for these changes of occuring, as well as their relative contributions to neoplastic progression.
Indeed, their own Figure 2 conceptually portrays expansion of stem cell lineages (a) and tumor cell clonal expansion (b), which display two separate patterns – linear versus branching selection. Their caption, however, muddles and confuses the distinction between these two patterns.