Related Experiment Video

Updated: Jun 12, 2026

A Modified In vitro Invasion Assay to Determine the Potential Role of Hormones, Cytokines and/or Growth Factors in Mediating Cancer Cell Invasion
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
PubMed
Abstract

Insights

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.

More Related Videos

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells09:03

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells

Published on: November 23, 2014

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...