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Updated: Jun 12, 2026
06:36
A Modified In vitro Invasion Assay to Determine the Potential Role of Hormones, Cytokines and/or Growth Factors in Mediating Cancer Cell Invasion
Published on: April 24, 2015
Nerve growth factor promotes breast cancer angiogenesis by activating multiple pathways
Rodrigue Romon1, Eric Adriaenssens, Chann Lagadec
1INSERM U908, F-59650 Villeneuve d'Ascq, France.
Molecular Cancer
|June 24, 2010
Summary
Nerve growth factor (NGF) stimulates breast cancer angiogenesis by activating TrkA, PI3K, and ERK pathways, leading to increased VEGF secretion. Targeting NGF and its pathways offers a promising new anti-angiogenic therapy strategy.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Current anti-angiogenic cancer therapies offer modest survival benefits, necessitating the discovery of novel molecular targets.
- Understanding the signaling pathways involved in angiogenesis is crucial for improving therapeutic efficacy.
Purpose of the Study:
- To investigate the role of nerve growth factor (NGF) in promoting breast cancer angiogenesis.
- To elucidate the molecular mechanisms underlying NGF-mediated angiogenesis.
Main Methods:
- In vivo studies using Matrigel plugs in immunodeficient mice to assess angiogenesis.
- In vitro assays examining endothelial cell invasion, cord formation, and monolayer permeability.
- Analysis of downstream signaling pathways including TrkA, PI3K, ERK, matrix metalloprotease 2, and nitric oxide synthase.
- Assessment of Vascular Endothelial Growth Factor (VEGF) secretion and the effect of its inhibition.
Main Results:
- Both recombinant NGF and endogenous NGF from breast cancer cells stimulated angiogenesis in vivo.
- NGF significantly enhanced endothelial cell invasion, cord formation, and permeability.
- NGF-induced invasion was mediated by its receptor TrkA and downstream PI3K/ERK signaling, activating MMP-2 and NOS.
- NGF increased VEGF secretion in endothelial and breast cancer cells, with VEGF inhibition reducing NGF-induced angiogenesis by approximately 50%.
Conclusions:
- Nerve growth factor (NGF) is a significant stimulator of angiogenesis in breast cancer.
- NGF and its activated signaling pathways represent potential therapeutic targets for anti-angiogenic strategies in breast cancer treatment.
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