Figure 5
The stress hormones/hypothalamic-pituitary-adrenal axis-dependent regulation of the IL-6/GSH interorgan cycling activity: a systemic mechanism promoting metastases growth. IL-6 (mainly of tumor origin) potentiates the release of pituitary ACTH. Stress hormones released by the suprarenal glands upregulate IL-6 expression and secretion by metastatic cells, which in turns increases GSH release from the liver. Tumor GGT degrades plasma GSH, providing extra Cys for metastic cell GSH synthesis. Other (unknown) tumor-derived molecular signals, acting as GSH release activators in other cancers, the role of tissue specific microenvironments, or the possible influence of tumor innervation in metastatic cell behavior, are open questions.