beta 3-Adrenoceptor, a novel player in the round-trip from neonatal diseases to cancer: Suggestive clues from embryo

The role of the beta-adrenoceptors (beta-ARs) in hypoxia-driven diseases has gained visibility after the demonstration that propranolol promotes the regression of infantile hemangiomas and ameliorates the signs of retinopathy of prematurity (ROP). Besides the role of beta 2-ARs, preclinical studies in ROP have also revealed that beta 3-ARs are upregulated by hypoxia and that they are possibly involved in retinal angiogenesis. In a sort of figurative round trip, peculiarities typical of ROP, where hypoxia drives retinal neovascularization, have been then translated to cancer, a disease equally characterized by hypoxia-driven angiogenesis. In this step, investigating the role of beta 3-ARs has taken advantage of the assumption that cancer growth uses a set of strategies in common with embryo development. The possibility that hypoxic induction of beta 3-ARs may represent one of the mechanisms through which primarily embryo (and then cancer, as an astute imitator) adapts to grow in an otherwise hostile environment, has grown evidence. In both cancer and embryo, beta 3-ARs exert 1 similar functions by exploiting a metabolic shift known as the Warburg effect, by acquiring resistance against xenobiotics, and by inducing a local immune tolerance. An additional potential role of beta 3-AR as a marker of sternness has been suggested by the finding that its antagonism induces cancer cell differentiation evoking that beta 3-ARs may help cancer to grow in a nonhospital environment, a strategy also exploited by embryos. From cancer, the round trip goes back to neonatal diseases for which new possible interpretative keys and potential pharmacological perspectives have been suggested.

Automated summary

The role of beta-adrenoceptors in hypoxia-driven diseases, such as infantile hemangiomas and retinopathy of prematurity, has been highlighted. The upregulation of beta 3-ARs by hypoxia in both cancer and embryo development suggests potential similarities in their functions.