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Recent Advances in Prolactin Research pp 265–280Cite as

A Positive Feedback Loop Between Prolactin and Stat5 Promotes Angiogenesis

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 846))

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.

This work was supported by UWCCC core grant P30 CA014520 and by award number I01BX000137 from the Biomedical Laboratory Research and Development Service of the VA Office of Research and Development. The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States government.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Wisconsin, 6051 WIMR, MC-2275, 1111 Highland Avenue, 53705, Madison, WI, USA

    Xinhai Yang & Andreas Friedl

  2. Pathology and Laboratory Medicine Service, Department of Veterans Affairs Medical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA

    Andreas Friedl

  3. University of Wisconsin Carbone Cancer Center, Madison, WI, USA

    Andreas Friedl

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  1. Xinhai Yang
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  2. Andreas Friedl
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Editors and Affiliations

  1. Department of Biological Sciences, University of Toledo, Toledo, Ohio, USA

    Maria Diakonova, PhD

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Yang, X., Friedl, A. (2015). A Positive Feedback Loop Between Prolactin and Stat5 Promotes Angiogenesis. In: Diakonova, PhD, M. (eds) Recent Advances in Prolactin Research. Advances in Experimental Medicine and Biology, vol 846. Springer, Cham. https://doi.org/10.1007/978-3-319-12114-7_12

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