The study by Shi et al offers compelling evidence that both stromal and tumour PAR-2 significantly influence pancreatic tumour growth and lymphatic metastatic potential. However, given the extreme variability in PAR-2 modes of activation, subsequent signalling, and the resulting cellular or secretory phenotype, the role of PAR-2 in pancreatic cancer and other cancers should be viewed as non-uniform and dependent (in large measure) on the individual tumour environment, as well as being very dependent on the experimental model used in the study.
Therefore, PAR-2 should be regarded less as a specific pro-carcinogenic/anti-cancer factor and more as an important and complex disease modifier with pharmacokinetic and pharmacodynamic properties that complicate possible therapeutic uses of PAR-2 inhibitors and activators in different diseases.