Access
To read this story in full you will need to login or make a payment (see right).
Article
Nature 444, 1032-1037 (21 December 2006) | doi:10.1038/nature05355; Received 17 June 2006; Accepted 16 October 2006
Open Innovation Challenges
-
Single-cell Analysis Platform
This Challenge is looking for novel approaches to analyzing changes at a single-cell level. This is...
-
Optimizing Sub-cellular Localization Tags
The Seeker is looking for methods to optimize sub-cellular localization tags for protein expression....
nature jobs
Admission for Research Scholars Program
- CDFD (Centre for DNA Fingerprinting and Diagnostics)
- Hyderabad, A.P. 500 001 India
Postdoctoral Positions
- Johns Hopkins University
- Baltimore, Maryland, USA
Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis
Irene Noguera-Troise1, Christopher Daly1, Nicholas J. Papadopoulos1, Sandra Coetzee1, Pat Boland1, Nicholas W. Gale1, Hsin Chieh Lin1, George D. Yancopoulos1 & Gavin Thurston1
- Regeneron Research Laboratories, 777 Old Saw Mill River Road, Tarrytown, New York 10591, USA
Correspondence to: Gavin Thurston1 Correspondence and requests for materials should be addressed to G.T. (Email: Gavin.Thurston@Regeneron.com).
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.
To read this story in full you will need to login or make a payment (see right).
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Promoting angiogenesis to a faultNature Biotechnology News and Views (01 Mar 2007)
Promoting angiogenesis to a faultNature Biotechnology News and Views (01 Mar 2007)
See all 6 matches for News And ViewsRESEARCH
Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesisNature Article (21 Dec 2006)
See all 21 matches for Research
