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A Positive Feedback Loop Between Prolactin and Stat5 Promotes Angiogenesis

  • Xinhai Yang
  • Andreas Friedl
Chapter
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

Proliferin Prolactin STAT5 Angiogenesis Tumor microenvironment 

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Xinhai Yang
    • 1
  • Andreas Friedl
    • 1
    • 2
    • 3
  1. 1.Department of Pathology and Laboratory MedicineUniversity of WisconsinMadisonUSA
  2. 2.Pathology and Laboratory Medicine Service, Department of Veterans Affairs Medical CenterWilliam S. Middleton Memorial Veterans HospitalMadisonUSA
  3. 3.University of Wisconsin Carbone Cancer CenterMadisonUSA

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