Autocrine glutamate signaling promotes glioma cell invasion.

Autocrine glutamate signaling promotes glioma cell invasion. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Autocrine glutamate signaling promotes glioma cell invasion. Abstract Text:

Susan A Lyons,W Joon Chung,Amy K Weaver,Toyin Ogunrinu,Harald Sontheimer,

Malignant gliomas have been shown to release glutamate, which kills surrounding brain cells, creating room for tumor expansion. This glutamate release occurs primarily via system xC, a Na+-independent cystine-glutamate exchanger. We show here, in addition, that the released glutamate acts as an essential autocrine/paracrine signal that promotes cell invasion. Specifically, chemotactic invasion and scrape motility assays each show dose-dependent inhibition of cell migration when glutamate release was inhibited using either S-(4)-CPG or sulfasalazine, both potent blockers of system xC. This inhibition could be overcome by the addition of exogenous glutamate (100 micromol/L) in the continued presence of the inhibitors. Migration/invasion was also inhibited when Ca2+-permeable alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPA-R) were blocked using GYKI or Joro spider toxin, whereas CNQX was ineffective. Ca2+ imaging experiments show that the released glutamate activates Ca2+-permeable AMPA-R and induces intracellular Ca2+ oscillations that are essential for cell migration. Importantly, glioma cells release glutamate in sufficient quantities to activate AMPA-Rs on themselves or neighboring cells, thus acting in an autocrine and/or paracrine fashion. System xC and the appropriate AMPA-R subunits are expressed in all glioma cell lines, patient-derived glioma cells, and acute patient biopsies investigated. Furthermore, animal studies in which human gliomas were xenographed into scid mice show that chronic inhibition of system xC-mediated glutamate release leads to smaller and less invasive tumors compared with saline-treated controls. These data suggest that glioma invasion is effectively disrupted by inhibiting an autocrine glutamate signaling loop with a clinically approved candidate drug, sulfasalazine, already in hand.

Autocrine glutamate signaling promotes glioma cell invasion. Publishing Authors By Initials

SA Lyons,WJ Chung,AK Weaver,T Ogunrinu,H Sontheimer,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Autocrine glutamate signaling promotes glioma cell invasion. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Cancer research

VOLUME: 67

Page Numbers: 9463-71

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 1

MONTH: Oct

YEAR: 2007

Autocrine glutamate signaling promotes glioma cell invasion. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984705

Autocrine glutamate signaling promotes glioma cell invasion. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Autocrine glutamate signaling promotes glioma cell invasion. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Autocrine glutamate signaling promotes glioma cell invasion.

AFFILIATION: Department of Neurobiology, Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Country: United States

AGENCY: United States NINDS

GRANT: R01NS052634

ACRONYM: NS

MEDLINETA: Cancer Res

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Autocrine glutamate signaling promotes glioma cell invasion Related Publications

• A glossary of modern health care economics: platitudes and principles gleaned from the first year's education of a new academic health care delivery center department head.
• A role for glutamate in growth and invasion of primary brain tumors.
• A role for ubiquitin in the spliceosome assembly pathway.
• A systematic review of juvenile-onset clinically amyopathic dermatomyositis.
• An inside job for siRNAs.
• An unexpected role for ion channels in brain tumor metastasis.
• Another view concerning the proposal to change the name of the American Academy of Dermatology.
• Antibodies inside our keratinocytes?
• Autocrine glutamate signaling promotes glioma cell invasion.
• BK channels are linked to inositol 1,4,5-triphosphate receptors via lipid rafts: a novel mechanism for coupling [Ca(2+)](i) to ion channel activation.
• Chronic penile ulceration in a 72-year-old man.
• ClC3 Is a Critical Regulator of the Cell Cycle in Normal and Malignant Glial Cells.
• Cutaneous lupus erythematosus: molecular and cellular basis of clinical findings.
• Cytoplasmic condensation is both necessary and sufficient to induce apoptotic cell death.
• Differential distribution of Kir4.1 in spinal cord astrocytes suggests regional differences in K+ homeostasis.
• Expression and function of water channels (aquaporins) in migrating malignant astrocytes.
• Extracellular glutamine is a critical modulator for regulatory volume increase in human glioma cells.
• Immunobiological significance of the Ro/SSA antigen-antibody system.
• Inhibition of transient receptor potential canonical channels impairs cytokinesis in human malignant gliomas.
• Questions answered and a $1 million question raised concerning lupus erythematosus tumidus: is routine laboratory surveillance testing during treatment with hydroxychloroquine for skin disease really necessary.
• Relative contribution of chloride channels and transporters to regulatory volume decrease in human glioma cells.
• Review: Statins reduce all-cause mortality in elderly patients with coronary heart disease.
• Role for calcium-activated potassium channels (BK) in growth control of human malignant glioma cells.
• Role of Kir4.1 channels in growth control of glia.
• Sarcoidal alopecia as a mimic of discoid lupus erythematosus.
• Suicide by advance directive?
• The anticardiolipin syndrome. A new way to slice an old pie, or a new pie to slice?