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Author Spotlight: Investigating Angiogenesis and Vessel Permeability Through a Modified Matrix Gel Plug Assay
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A positive feedback loop between prolactin and STAT5 promotes angiogenesis.
1Department of Pathology and Laboratory Medicine, University of Wisconsin, 6051 WIMR, MC-2275, 1111 Highland Avenue, 53705, Madison, WI, USA, afriedl@wisc.edu.
Advances in Experimental Medicine and Biology
|December 5, 2014
Summary
Prolactin (PRL) signaling activates signal transducers and activators of transcription 5 (STAT5) in endothelial cells, promoting tumor angiogenesis. Inhibiting PRL signaling offers a potential therapeutic strategy for disrupting tumor blood vessel formation.
Area of Science:
- Cell Biology
- Molecular Biology
- Oncology
Background:
- Signal transduction pathways regulating angiogenesis are not fully understood.
- Fibroblast growth factors activate signal transducers and activators of transcription (STAT) family members.
- STAT5 activation is crucial for endothelial cell migration, invasion, and tube formation.
Purpose of the Study:
- To elucidate the role of prolactin (PRL) and its receptor (PRLR) in STAT5-mediated endothelial cell functions.
- To investigate the mechanisms by which PRL signaling contributes to tumor angiogenesis.
- To explore the therapeutic potential of targeting PRL signaling in cancer.
Main Methods:
- Investigated STAT5 activation in endothelial cells.
- Examined the requirement of proliferin-1 (PLF1) in mice and PRL in humans for STAT5 effects.
- Analyzed PRL receptor (PRLR) activation and downstream signaling (MAPK).
- Discussed in vivo mechanisms of PRL action in the tumor microenvironment.
Main Results:
- STAT5 activation is necessary and sufficient for endothelial cell migration, invasion, and tube formation.
- PRL/PRLR signaling induces MAPK and STAT5 activation, creating a positive feedback loop.
- Endothelial cell-derived PRL contributes to the tumor microenvironment's PRL concentration.
- PRL can stimulate tumor angiogenesis through autocrine, paracrine, and endocrine pathways.
Conclusions:
- PRL signaling is a key regulator of endothelial cell functions essential for angiogenesis.
- PRL promotes tumor angiogenesis via multiple signaling pathways.
- Targeting PRL signaling represents a promising therapeutic strategy for inhibiting tumor angiogenesis.
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