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  • Tumor-Derived Factors and Reduced p53 Promote Endothelial Cell Centrosome Over-Duplication.

Tumor-Derived Factors and Reduced p53 Promote Endothelial Cell Centrosome Over-Duplication.

PloS one (2016-12-16)
Zhixian Yu, Kevin P Mouillesseaux, Erich J Kushner, Victoria L Bautch
ABSTRACT

Approximately 30% of tumor endothelial cells have over-duplicated (>2) centrosomes, which may contribute to abnormal vessel function and drug resistance. Elevated levels of vascular endothelial growth factor A induce excess centrosomes in endothelial cells, but how other features of the tumor environment affect centrosome over-duplication is not known. To test this, we treated endothelial cells with tumor-derived factors, hypoxia, or reduced p53, and assessed centrosome numbers. We found that hypoxia and elevated levels of bone morphogenetic protein 2, 6 and 7 induced excess centrosomes in endothelial cells through BMPR1A and likely via SMAD signaling. In contrast, inflammatory mediators IL-8 and lipopolysaccharide did not induce excess centrosomes. Finally, down-regulation in endothelial cells of p53, a critical regulator of DNA damage and proliferation, caused centrosome over-duplication. Our findings suggest that some tumor-derived factors and genetic changes in endothelial cells contribute to excess centrosomes in tumor endothelial cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
TWEEN® 20, viscous liquid, suitable for cell culture
Sigma-Aldrich
MISSION® esiRNA, targeting human BMPR2
Sigma-Aldrich
MISSION® esiRNA, targeting human BMPR1A