title: A positive feedback loop between prolactin and STAT5 promotes angiogenesis.
abstract: The signal transduction events that orchestrate cellular activities required for angiogenesis remain incompletely understood. We and others recently described that proangiogenic mediators such as fibroblast growth factors can activate members of the signal transducers and activators of transcription (STAT) family. STAT5 activation is necessary and sufficient to induce migration, invasion and tube formation of endothelial cells. STAT5 effects on endothelial cells require the secretion of the prolactin (PRL) family member proliferin-1 (PLF1) in mice and PRL in humans. In human endothelial cells, PRL activates the PRL receptor (PRLR) resulting in MAPK and STAT5 activation, thus closing a positive feedback loop. In vivo, endothelial cell-derived PRL is expected to combine with PRL of tumor cell and pituitary origin to raise the concentration of this polypeptide hormone in the tumor microenvironment. Thus, PRL may stimulate tumor angiogenesis via autocrine, paracrine, and endocrine pathways. The disruption of tumor angiogenesis by interfering with PRL signaling may offer an attractive target for therapeutic intervention.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin, 6051 WIMR, MC-2275, 1111 Highland Avenue, 53705, Madison, WI, USA, afriedl@wisc.edu.
authors.forename: Xinhai
authors.initials: X
authors.lastname: Yang
authors.forename: Andreas
authors.initials: A
authors.lastname: Friedl
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D011388:Prolactin / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D050799:STAT5 Transcription Factor; D005346:Fibroblast Growth Factors; D011388:Prolactin