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

Authors

• Zhixian Yu, The University of North Carolina at Chapel Hill
• Kevin P. Mouillesseaux, The University of North Carolina at Chapel Hill
• Erich J. Kushner, The University of North Carolina at Chapel Hill, University of Denver
• Victoria L. Bautch, McAllister Heart Institute, The University of North Carolina at Chapel Hill

Publication Date

12-15-2016

Document Type

Article

Organizational Units

College of Natural Science and Mathematics, Biological Sciences

Keywords

Endothelial cells, Abnormal vessel function, Hypoxia, Over-duplicated, Centrosomes

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.

Copyright Date

12-15-2016

Copyright Statement / License for Reuse

This work is licensed under a Creative Commons Attribution 4.0 International License.

Rights Holder

The Authors

Provenance

Received from author

File Format

application/pdf

Language

English (eng)

Extent

13 pgs

File Size

1031 KB

Publication Statement

Copyright is held by the authors. User is responsible for all copyright compliance. This article was originally published as:

Yu, Z., Mouillesseaux, K. P., Kushner, E. J., & Bautch, V. L. (2016). Tumor-derived factors and reduced p53 promote endothelial cell centrosome over-duplication. PloS One, 11(12), 1-13. DOI: 10.1371/journal.pone.0168334

ISSN

1932-6203

Recommended Citation

Yu, Z., Mouillesseaux, K. P., Kushner, E. J., & Bautch, V. L. (2016). Tumor-derived factors and reduced p53 promote endothelial cell centrosome over-duplication. PloS One, 11(12), 1-13. DOI: 10.1371/journal.pone.0168334

DOI Link

https://doi.org/10.1371/journal.pone.0168334