Linked Life Data

18539131

Source:http://linkedlifedata.com/resource/pubmed/id/18539131

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-8-13
pubmed:abstractText
Matrix metalloproteinase 9 (MMP-9) plays a critical role in digesting the extracellular matrix and has a vital function in tumor metastasis and invasion; this protease activity is significantly increased in non-small cell lung cancers. The sodium hydrogen exchanger isoform 1 (NHE1) functions as a focal point for signal coordination and cytoskeletal reorganization. NHE1 is thought to play a central role in establishing signaling components at the leading edge of a migrating cell. Therefore, we studied the relationship between NHE1 and MMP-9 activity in Chinese hamster lung fibroblasts (CCL39) stimulated with phenylephrine (PE). We show that PE increases MMP-9 gelatinolytic activity in CCL39 cells. The inhibition of phospholipase D (PLD) signaling abrogated PE-induced MMP-9 activity. The role of PLD as an essential signaling intermediate was confirmed when the addition of permeable phosphatidic acid increased MMP-9 activity in the same cells. PE-induced invasion was increased 1.9-fold over controls and the PE response was lost when 1-butanol was used to block PLD signaling. Cells pre-treated with the NHE1 inhibitor, 5-(N-ethyl-N-isopropyl) amiloride (EIPA) prior to PE addition resulted in a notable decrease in MMP-9 activation and cell invasion as compared to untreated PE-stimulated cells. CCL39 NHE1 null cells demonstrated no increase in MMP-9 protease activity or cell invasion in response to PE treatment. Reconstitution of NHE1 expression recovered the PE-induced activation of protease activity and cell invasion. MMP-9 processing was altered in cells expressing a proton transport defective NHE1 but retained the ability to respond to PE. Conversely, cells expressing an ezrin, radixin, moesin (ERM)-binding deficient NHE1 had a lower MMP-9 activity and the protease did not respond to PE addition. Parallel studies on NCI-H358 non-small cell lung cancer (NSCL) cells showed that PE stimulated both MMP-9 activity and cell invasion in an NHE1 dependent manner. This work describes for the first time a PE-induced relationship between NHE1 and MMP-9 and a new potential mechanism by which NHE1 could promote tumor formation and metastasis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1096-0384
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
477
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
60-6
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18539131-Adrenergic alpha-1 Receptor Agonists, pubmed-meshheading:18539131-Adrenergic alpha-Agonists, pubmed-meshheading:18539131-Animals, pubmed-meshheading:18539131-Blotting, Western, pubmed-meshheading:18539131-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:18539131-Cell Line, pubmed-meshheading:18539131-Cell Line, Tumor, pubmed-meshheading:18539131-Cricetinae, pubmed-meshheading:18539131-Cricetulus, pubmed-meshheading:18539131-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:18539131-Enzyme Activation, pubmed-meshheading:18539131-Fibroblasts, pubmed-meshheading:18539131-Glycerophospholipids, pubmed-meshheading:18539131-Humans, pubmed-meshheading:18539131-Lung Neoplasms, pubmed-meshheading:18539131-Matrix Metalloproteinase 9, pubmed-meshheading:18539131-Neoplasm Invasiveness, pubmed-meshheading:18539131-Phenylephrine, pubmed-meshheading:18539131-Phospholipase D, pubmed-meshheading:18539131-Receptors, Adrenergic, alpha-1, pubmed-meshheading:18539131-Sodium-Hydrogen Antiporter
pubmed:year
2008
pubmed:articleTitle
Sodium hydrogen exchanger and phospholipase D are required for alpha1-adrenergic receptor stimulation of metalloproteinase-9 and cellular invasion in CCL39 fibroblasts.
pubmed:affiliation
Departments of Chemistry and Biosciences, Minnesota State University Moorhead, Hagen Hall, Moorhead, MN 56563, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural