NDLI: Epidermal growth factor plays a crucial role in mitogenic regulation of human brain tumor stem cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Inagaki, Akihito Ikegame, Yuka Aoki, Hitomi Nakashima, Shigeru Kunisada, Takahiro Iwama, Toru Soeda, Akio Oka, Naoki Yoshimura, Shin-ichi
Description	Author Affiliation: Soeda A ( Department of Neurosurgery, Tissue and Organ Development Regeneration and Advanced Medical Science, and Cell Signaling, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan. akio.soeda@gmail.com)
Abstract	A cancer stem cell population in malignant brain tumors takes an essential part in brain tumor initiation, growth, and recurrence. Growth factors, such as epidermal growth factor, fibroblast growth factor-2, vascular endothelial growth factor, platelet-derived growth factor, and hepatocyte growth factor, are shown to support the proliferation of neural stem cells and also may play key roles in gliomagenesis. However, the responsible growth factor(s), which controls maintenance of brain tumor stem cells, is not yet uncovered. We have established three cancer stem cell lines from human gliomas. These cells were immunoreactive with the neuronal progenitor markers, nestin and CD133, and established tumors that closely resembled the features of original tumor upon transplantation into mouse brain. Three cell lines retained their self-renewal ability and proliferation only in the presence of epidermal growth factor (>2.5 ng/ml). In sharp contrast, other growth factors, including fibroblast growth factor-2, failed to support maintenance of these cells. The tyrosine kinase inhibitors of epidermal growth factor signaling (AG1478 and gefitinib) suppressed the proliferation and self-renewal of these cells. Gefitinib inhibited phosphorylation of epidermal growth factor receptor as well as Akt kinase and extracellular signal-regulated kinase 1/2. Flow cytometric analysis revealed that epidermal growth factor concentration-dependently increased the population of CD133-positive cells. Gefitinib significantly reduced CD133-positive fractions and also induced their apoptosis. These results indicate that maintenance of human brain tumor stem cells absolutely requires epidermal growth factor and that tyrosine kinase inhibitors of epidermal growth factor signaling potentially inhibit proliferation and induce apoptosis of these cells.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	16
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-04-18
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Brain Neoplasms Metabolism Epidermal Growth Factor Physiology Gene Expression Regulation, Neoplastic Stem Cells Antigens, CD Biosynthesis Enzyme Inhibitors Pharmacology Glycoproteins Intercellular Signaling Peptides And Proteins Models, Biological Peptides Phosphorylation Protein-Tyrosine Kinases Antagonists & Inhibitors Quinazolines Signal Transduction Tumor Cells, Cultured Tyrphostins Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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