Abstract
Ceruloplasmin (glycosylphosphatidylinositol-linked ferroxidase associated with normal astrocytes) can also be secreted by glioma cells, where its function is unknown. Ceruloplasmin is not only present in glioma cells and in human glioma specimens but also is enriched in highly malignant glioma stem-like cells. Hyaluronan is a large extracellular glycosaminoglycan that enhances malignant glioma behaviors by interacting with CD44 receptors and by downstream activation of signaling proteins and transporters associated with malignancy. We examined the relationship between hyaluronan and ceruloplasmin expression in glioma stem-like cells. Antagonism of hyaluronan interactions with short-fragment hyaluronan oligomers decreased ceruloplasmin expression in parental and stem-like glioma cells in vivo and in cell culture, implying that hyaluronan regulates ceruloplasmin expression. Further gain and loss-of-function studies are needed to fully define the relationship between hyaluronan and ceruloplasmin, and ceruloplasmin's effect on malignant behaviors.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biomarkers, Tumor / metabolism
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Brain Neoplasms / drug therapy
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Brain Neoplasms / genetics
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Brain Neoplasms / metabolism*
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Cell Line, Tumor
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Cell Transformation, Neoplastic / drug effects
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism
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Ceruloplasmin / drug effects
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Ceruloplasmin / metabolism*
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Disease Models, Animal
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Down-Regulation / drug effects
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Down-Regulation / physiology
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Drug Resistance, Neoplasm / genetics
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Extracellular Matrix / metabolism
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Female
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Glioma / genetics
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Glioma / metabolism*
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Glioma / physiopathology
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Humans
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Hyaluronan Receptors / drug effects
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Hyaluronan Receptors / metabolism
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Hyaluronic Acid / metabolism*
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Hyaluronic Acid / pharmacology
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Neoplasm Invasiveness / genetics
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Neoplastic Stem Cells / drug effects
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Neoplastic Stem Cells / metabolism*
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Rats
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Rats, Sprague-Dawley
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Spinal Cord Neoplasms / drug therapy
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Spinal Cord Neoplasms / genetics
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Spinal Cord Neoplasms / metabolism
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Stem Cells / drug effects
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Stem Cells / metabolism*
Substances
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Biomarkers, Tumor
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Hyaluronan Receptors
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Hyaluronic Acid
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Ceruloplasmin