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.
Keywords: S100A8, SAA3, TLR4, metastasis, pre-metastasis, inflammation, homeostasis
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