Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis

Irene Noguera-Troise, Christopher Daly, Nicholas J. Papadopoulos, Sandra Coetzee, Pat Boland, Nicholas W. Gale, Hsin Chieh Lin, George D. Yancopoulos and Gavin Thurston ()
Additional contact information
Irene Noguera-Troise: Regeneron Research Laboratories
Christopher Daly: Regeneron Research Laboratories
Nicholas J. Papadopoulos: Regeneron Research Laboratories
Sandra Coetzee: Regeneron Research Laboratories
Pat Boland: Regeneron Research Laboratories
Nicholas W. Gale: Regeneron Research Laboratories
Hsin Chieh Lin: Regeneron Research Laboratories
George D. Yancopoulos: Regeneron Research Laboratories
Gavin Thurston: Regeneron Research Laboratories

Nature, 2006, vol. 444, issue 7122, 1032-1037

Abstract: Abstract Tumour growth requires accompanying expansion of the host vasculature, with tumour progression often correlated with vascular density. Vascular endothelial growth factor (VEGF) is the best-characterized inducer of tumour angiogenesis. We report that VEGF dynamically regulates tumour endothelial expression of Delta-like ligand 4 (Dll4), which was previously shown to be absolutely required for normal embryonic vascular development. To define Dll4 function in tumour angiogenesis, we manipulated this pathway in murine tumour models using several approaches. Here we show that blockade resulted in markedly increased tumour vascularity, associated with enhanced angiogenic sprouting and branching. Paradoxically, this increased vascularity was non-productive—as shown by poor perfusion and increased hypoxia, and most importantly, by decreased tumour growth—even for tumours resistant to anti-VEGF therapy. Thus, VEGF-induced Dll4 acts as a negative regulator of tumour angiogenesis; its blockade results in a striking uncoupling of tumour growth from vessel density, presenting a novel therapeutic approach even for tumours resistant to anti-VEGF therapies.

Date: 2006
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature05355 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:444:y:2006:i:7122:d:10.1038_nature05355

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature05355

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().