A Concept of Homeostatic Inflammation Provided by Endogenous TLR4 Agonists that Function Before and After Danger Signal for Metastasis

Provoked by the discovery of metastasis-inducing endogenous ligands of TLR4 that has been recognized as a sensor for extrinsic pathogens, I propose an extended concept for danger signal that originally meant sentinels over tissue destruction by cancer. The so-called “homeostatic inflammation” concept includes signals before destruction actually takes place such as those in pre-metastatic microenvironment and possibly even in physiological conditions. It is orchestrated by tight cross-talks between growth factor and chemokine signaling.