Nerve growth factor promotes breast cancer angiogenesis by activating multiple pathways

Molecular Cancer

Research

Xuefen Le Bourhis¹  Chann Lagadec¹  Hubert Hondermarck¹  Emmanuelle Germain¹  Rodrigue Romon¹  Eric Adriaenssens² 

[1] INSERM U908, F-59650, Villeneuve d'Ascq, France;USTL, F-59650, Villeneuve d'Ascq, France;Univ Lille Nord de France, F-59000, Lille, France;USTL, F-59650, Villeneuve d'Ascq, France;CNRS UMR 8161, Institut Pasteur de Lille, F-59800, Lille, France;Univ Lille Nord de France, F-59000, Lille, France;

关键词: Nitric Oxide;    Vascular Endothelial Growth Factor;    Nerve Growth Factor;    Human Umbilical Vein Endothelial Cell;    Epithelial Ovarian Cancer Cell;   

DOI  :  10.1186/1476-4598-9-157

 received in 2010-03-26, accepted in 2010-06-22,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundAlthough several anti-angiogenic therapies have been approved in the treatment of cancer, the survival benefits of such therapies are relatively modest. Discovering new molecules and/or better understating signaling pathways of angiogenesis is therefore essential for therapeutic improvements. The objective of the present study was to determine the involvement of nerve growth factor (NGF) in breast cancer angiogenesis and the underlying molecular mechanisms.ResultsWe showed that both recombinant NGF and NGF produced by breast cancer cells stimulated angiogenesis in Matrigel plugs in immunodeficient mice. NGF strongly increased invasion, cord formation and the monolayer permeability of endothelial cells. Moreover, NGF-stimulated invasion was under the control of its tyrosine kinase receptor (TrkA) and downstream signaling pathways such as PI3K and ERK, leading to the activation of matrix metalloprotease 2 and nitric oxide synthase. Interestingly, NGF increased the secretion of VEGF in both endothelial and breast cancer cells. Inhibition of VEGF, with a neutralizing antibody, reduced about half of NGF-induced endothelial cell invasion and angiogenesis in vivo.ConclusionsOur findings provided direct evidence that NGF could be an important stimulator for breast cancer angiogenesis. Thus, NGF, as well as the activated signaling pathways, should be regarded as potential new targets for anti-angiogenic therapy against breast cancer.

【 授权许可】

Unknown   
© Romon et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.