Abstract
Tumorigenesis requires interactions between tumor progenitors and their microenvironment. We found that low cAMP levels were sufficient for tumorigenesis in a mouse model of Neurofibromatosis-1 (NF1)-associated optic pathway glioma (OPG). We hypothesized that the distinct pattern of glioma in NF1 reflected spatiotemporal differences in CXCL12 effects on cAMP levels. Thus, we sought to alter the pattern of gliomagenesis through manipulation of CXCL12-CXCR4 pathway activation in Nf1 OPG mice. Forced CXCL12 expression induced glioma at a low frequency. Further, treatment of Nf1 OPG mice with AMD3100, a CXCR4 antagonist, did not attenuate glioma growth. Thus, it appears, CXCL12 alone cannot promote gliomagenesis in NF1 mice.
(c) 2010 Elsevier B.V. All rights reserved.
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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Brain Neoplasms / genetics*
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Brain Neoplasms / immunology
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Brain Neoplasms / metabolism*
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Cell Line
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / immunology
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Cell Transformation, Neoplastic / metabolism
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Chemokine CXCL12 / biosynthesis
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Chemokine CXCL12 / genetics
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Chemokine CXCL12 / physiology*
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Disease Models, Animal
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Gene Expression Regulation, Neoplastic / immunology
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Humans
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Mice
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Mice, Neurologic Mutants
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Neurofibromin 1 / genetics
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Neurofibromin 1 / physiology*
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Optic Nerve Glioma / genetics*
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Optic Nerve Glioma / immunology
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Optic Nerve Glioma / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Signal Transduction / immunology
Substances
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Chemokine CXCL12
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Cxcl12 protein, mouse
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Neurofibromin 1