Tumor-Derived Factors and Reduced p53 Promote Endothelial Cell Centrosome Over-Duplication
Endothelial cells, Abnormal vessel function, Hypoxia, Over-duplicated, Centrosomes
College of Natual Science and Mathematics, Biological Sciences
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.
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Yu, Zhixian, et al. “Tumor-Derived Factors and Reduced p53 Promote Endothelial Cell Centrosome Over-Duplication.” PloS One, vol. 11, no. 12, 2016, p. e0168334. doi: 10.1371/journal.pone.0168334.