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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1993-3-23
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pubmed:abstractText |
Expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) by metastatic Lewis lung carcinoma cells (LLC-LN7) was previously shown to contribute to the maintenance of phenotypic characteristics associated with an increased capacity to metastasize. In the present study, pre-incubation of LLC-LN7 cells with neutralizing anti-GM-CSF antibodies diminished the capacity of the tumor cells to form experimental metastases after i.v. inoculation, while pre-incubation with recombinant GM-CSF (rGM-CSF) increased formation of metastases. In the presence of rGM-CSF, the LLC-LN7 cells exhibited an increased capacity to migrate, invade through a reconstituted basement membrane, and adhere to lung tissue. Studies to identify the signal transduction pathway through which GM-CSF enhanced the in vitro metastatic properties of the LLC-LN7 tumor cells implicated protein kinase A (PKA). Signaling through PKA was suggested by the demonstration that the stimulation of tumor-cell motility by GM-CSF was blocked in the presence of the adenylate cyclase inhibitor nicotinic acid, or the PKA inhibitors A3 or KT5720. In addition, the role of PKA as a signaling mechanism for GM-CSF was assessed by using REV-LN7 cells, which are LLC-LN7 cells that have been stably transfected with an expression vector encoding a mutant PKA RI alpha subunit and which, in turn, express a cAMP-resistant PKA. Adherence and invasion by the PKA-defective REV-LN7 cells were not stimulated by rGM-CSF, contrasting with the stimulation observed for wild-type LLC-LN7 cells. These data suggest that rGM-CSF can further enhance the in vitro metastatic characteristics of LLC-LN7 tumor cells and that this is dependent on signal transduction through PKA.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0020-7136
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
20
|
pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
667-71
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8436441-Animals,
pubmed-meshheading:8436441-Carcinoma,
pubmed-meshheading:8436441-Cell Adhesion,
pubmed-meshheading:8436441-Cell Movement,
pubmed-meshheading:8436441-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:8436441-Lung Neoplasms,
pubmed-meshheading:8436441-Mice,
pubmed-meshheading:8436441-Mice, Inbred C57BL,
pubmed-meshheading:8436441-Neoplasm Invasiveness,
pubmed-meshheading:8436441-Neoplasm Metastasis,
pubmed-meshheading:8436441-Neoplasms, Experimental,
pubmed-meshheading:8436441-Protein Kinases,
pubmed-meshheading:8436441-Receptors, Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:8436441-Signal Transduction
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pubmed:year |
1993
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pubmed:articleTitle |
Granulocyte-macrophage colony-stimulating factor stimulates the metastatic properties of Lewis lung carcinoma cells through a protein kinase A signal-transduction pathway.
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pubmed:affiliation |
Department of Research Services, Hines V.A. Hospital, Hines, IL 60141.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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