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Molecular therapies targeting Vegf signaling combined with chemotherapy or other drugs exhibit promising results to improve efficacy of treatment. Dopamine has been recently proposed to be a novel safe anti\u2010angiogenic drug that stabilizes abnormal blood vessels and increases therapeutic efficacy. Here, we aimed to identify a treatment to normalize tumoral vessels and restore normal blood perfusion in tumor tissue with a Vegf receptor inhibitor and\/or a ligand of dopamine G protein\u2010coupled receptor D2 (D2R). Dopamine, <jats:italic>via<\/jats:italic> its action on D2R, is an endogenous effector of the pituitary gland, and we took advantage of this system to address this question. We have used a previously described Hmga2\/T mouse model developing haemorrhagic prolactin\u2010secreting adenomas. In mutant mice, blood vessels are profoundly altered in tumors, and an aberrant arterial vascularization develops leading to the loss of dopamine supply. D2R agonist treatment blocks tumor growth, induces regression of the aberrant blood supply and normalizes blood vessels. A chronic treatment is able to restore the altered balance between pro\u2010 and anti\u2010angiogenic factors. Remarkably, an acute treatment induces an upregulation of the stabilizing factor Angiopoietin 1. An anti\u2010Vegf therapy is also effective to restrain tumor growth and improves vascular remodeling. Importantly, only the combination treatment suppresses intratumoral hemorrhage and restores blood vessel perfusion, suggesting that it might represent an attractive therapy targeting tumor vasculature. Similar strategies targeting other ligands of GPCRs involved in angiogenesis may identify novel therapeutic opportunities for cancer.<\/jats:p>","DOI":"10.1002\/ijc.30628","type":"journal-article","created":{"date-parts":[[2017,2,2]],"date-time":"2017-02-02T23:27:36Z","timestamp":1486078056000},"page":"2150-2161","source":"Crossref","is-referenced-by-count":29,"title":["Complementary actions of dopamine D2 receptor agonist and anti\u2010vegf therapy on tumoral vessel normalization in a transgenic mouse model"],"prefix":"10.1002","volume":"140","author":[{"given":"Norbert","family":"Chauvet","sequence":"first","affiliation":[{"name":"CNRS, UMR\u20105203, Institut de G\u00e9nomique Fonctionnelle, D\u00e9partement de Physiologie Montpellier F\u201034094 France"},{"name":"INSERM, U1191 Montpellier F\u201034094 France"},{"name":"Universit\u00e9 de Montpellier, UMR\u20105203 Montpellier F\u201034094 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