Reference : The Antiangiogenic 16K Prolactin Impairs Functional Tumor Neovascularization by Inhibiti...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/105341
The Antiangiogenic 16K Prolactin Impairs Functional Tumor Neovascularization by Inhibiting Vessel Maturation
English
Nguyen, Ngoc-Quynh-Nhu mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
Castermans, Karolien [> >]
Berndt, Sarah [> >]
Herkenne, Stéphanie mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
Tabruyn, Sébastien mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
Blacher, Silvia mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Lion, Michelle mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
Noël, Agnès mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Martial, Joseph mailto [Université de Liège - ULg > Département des sciences de la vie > Département des sciences de la vie >]
Struman, Ingrid mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
7-Nov-2011
PLoS ONE
Public Library of Science
6
11
e27318-27318
Yes (verified by ORBi)
International
1932-6203
San Franscisco
CA
[en] Background: Angiogenesis, the formation of new blood vessels from existing vasculature, plays an essential role in tumor growth, invasion, and metastasis. 16K hPRL, the antiangiogenic 16-kDa N-terminal fragment of human prolactin was shown to prevent tumor growth and metastasis by modifying tumor vessel morphology.
Methodology/Principal Findings: Here we investigated the effect of 16K hPRL on tumor vessel maturation and on the related signaling pathways. We show that 16K hPRL treatment leads, in a murine B16-F10 tumor model, to a dysfunctional tumor vasculature with reduced pericyte coverage, and disruption of the PDGF-B/PDGFR-B, Ang/Tie2, and Delta/Notch pathways. In an aortic ring assay, 16K hPRL impairs endothelial cell and pericyte outgrowth from the vascular ring. In addition, 16K hPRL prevents pericyte migration to endothelial cells. This event was independent of a direct inhibitory effect of 16K hPRL on pericyte viability, proliferation, or migration. In endothelial cell-pericyte cocultures, we found 16K hPRL to disturb Notch signaling.
Conclusions/Significance: Taken together, our data show that 16K hPRL impairs functional tumor neovascularization by inhibiting vessel maturation and for the first time that an endogenous antiangiogenic agent disturbs Notch signaling. These findings provide new insights into the mechanisms of 16K hPRL action and highlight its potential for use in anticancer therapy.
Researchers
http://hdl.handle.net/2268/105341
10.1371/journal.pone.0027318
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0027318
FP7 ; 201279 - MICROENVIMET - Understanding and fighting metastasis by modulating the tumour microenvironment through interference with the protease network.

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