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Method for Novel Anti-Cancer Drug Development using Tumor Explants of Surgical Specimens
Published on: July 29, 2011
Notch, neural stem cells, and brain tumors.
T J Pierfelice1, K C Schreck, C G Eberhart
1Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Cold Spring Harbor Symposia on Quantitative Biology
|November 22, 2008
Summary
The Notch pathway is crucial for brain development, regulating neural stem cells. Aberrant Notch signaling in brain tumors suggests it may drive cancer growth, offering therapeutic targets.
Area of Science:
- Neuroscience
- Developmental Biology
- Oncology
Background:
- The Notch pathway is essential for cell-fate specification in the developing mammalian nervous system.
- Notch signaling regulates neural stem/progenitor cell pools, influencing neurogenesis and gliogenesis.
- Canonical Notch cascade is active in neural stem cells but reduced in neurogenic progenitors.
Purpose of the Study:
- To explore the role of Notch signaling in brain tumor biology.
- To investigate the similarities between brain tumor stem-like cells and neural stem/progenitor cells.
- To understand Notch's function in both neoplastic and non-neoplastic stem/progenitor populations.
Main Methods:
- Review of existing literature on Notch pathway function in neural development and brain tumors.
- Comparative analysis of Notch signaling in stem/progenitor cells versus tumor-initiating cells.
- Examination of Notch receptor expression in various brain tumor types.
Main Results:
- Notch receptors are overexpressed in multiple brain tumor types.
- Notch signaling may play a role in initiating some brain tumors.
- Brain tumor stem-like cells share characteristics with neural stem/progenitor cells and may depend on Notch for growth.
Conclusions:
- Notch signaling is implicated in both normal brain development and brain tumor pathogenesis.
- Understanding Notch's role in stem/progenitor cells is key to advancing developmental biology and brain tumor therapies.
- Targeting Notch signaling presents a potential therapeutic strategy for brain tumors.
Related Concept Videos
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:26Stem Cell Niche
The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
01:15Neurogenesis and Regeneration of Nervous Tissue
In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...