Figure 8.

Cartoon illustrating heterogeneity in PANC-1 cells with respect to EMT/MET phenotypes. (A) Principal induction of EMT (red lines), e.g., by growth factors such as TGFβ, or induction of MET (blue lines), e.g., by proinflammatory cytokines INFγ, IL1β and TNFα (IIT), and the associated changes in marker expression (↑ and ↓ denote up- and downregulation, respectively). (B) Schematic representation of the different EMT phenotypes present in parental cultures of PANC-1 based on marker expression and functional properties of the six clones. The stippled lines denote the principal ability of the hybrid phenotypes for further dedifferentiation towards a more complete/extreme M phenotype, or redifferentiation to the previous E state. With regard to the latter event, it is currently unclear whether IIT treatment can reprogram MIA PaCa-2 cells to an extreme E phenotype or merely to one of several hybrid E/M states (denoted by question marks). It also remains to be investigated whether all of the hybrid E/M phenotypes present in PANC1 cultures respond to TGFβ1 or IIT with induction of these differentiation events and whether their concentration or duration of exposure is critical. BxPC-3 cells are unlikely to harbor E/M or M-type cells as they are VIM negative, while MIA PaCa-2 cells are unlikely to contain E or E/M-type cells as they are ECAD negative.