Ghrelin and tumors.

Since the original discovery of ghrelin and, subsequently, obestatin (the alternative product of the ghrelin gene), a major interest has been devoted to the investigation of their central and peripheral activities in physiological conditions as well as on their role in metabolic diseases. However, several studies with different methodological approaches variably identified ghrelin and obestatin synthesis and secretion in several neoplastic conditions, including neuroendocrine and non-neuroendocrine cancers of various sites. Moreover, in vitro studies showed the capability of ghrelin to modulate tumor cell functions such as cell proliferation, apoptosis and invasiveness, although with variable and even paradoxical effects in different cell models. Interestingly, in most studies, it was demonstrated that ghrelin exerts its pro- or antineoplastic properties by means of receptors other than GHSR1a, that still need to be identified. However, the possible usefulness of the modulation of the ghrelin/obestatin axis in neoplastic conditions using either synthetic agonists or antagonists, though interesting in perspective, is still far from clinical applicability, and probably more related to the regulation of specific metabolic pathways in tumor cells, including lipid and carbohydrate use, than to the specific modulation of cell proliferation.