Linked Life Data

17121915

Source:http://linkedlifedata.com/resource/pubmed/id/17121915

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-11-23
pubmed:abstractText
Insulin-like growth factor binding protein-3 (IGFBP-3), a major IGF-binding protein in human serum, regulates the growth of non-small cell lung cancer (NSCLC) cells through IGF-dependent and IGF-independent mechanisms. However, the role of IGFBP-3 in lung cancer metastasis is not well known. In the present study, we showed that noncytotoxic doses of adenoviral or recombinant IGFBP-3 significantly decreased the migration and invasion of H1299 and A549 NSCLC cells. Furthermore, treatment of human lung fibroblasts with recombinant IGFBP-3 suppressed their ability to stimulate the invasion of H1299 cells. Overexpression of IGFBP-3 markedly reduced lung metastasis of A549 cells in an experimental animal model system and prolonged the survival time of the animals. Urokinase-type plasminogen activator (uPA) inhibitor treatment or uPA small interfering RNA transfection of A549 and H1299 cells resulted in a significant decrease in invasion. Corresponding ELISA, Western blot, gelatin zymogram, and semiquantitative reverse transcription-PCR analyses revealed that IGFBP-3 reduced the expression of uPA mRNA through IGF-independent mechanisms. The specific role of uPA in anti-invasive activity of IGFBP-3 was further confirmed in NSCLC cells, in which uPA expression/activity was suppressed by the transfection with synthetic small interfering RNA or by the treatment with uPA inhibitor or induced by the infection with an adenoviral vector. IGFBP-3 also decreased the expression/activity of matrix metalloproteinase-2 through IGF-dependent but uPA-independent pathways. Taken together, our data suggest that IGFPB-3 effectively block uPA- and matrix metalloproteinase-2-stimulated invasion pathways, ultimately reducing lung cancer cell metastasis. Our findings indicate that IGFBP-3 may be a promising anti-invasive and antimetastatic therapeutic agent in lung cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2685-95
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17121915-Animals, pubmed-meshheading:17121915-Antineoplastic Agents, pubmed-meshheading:17121915-Cell Line, Tumor, pubmed-meshheading:17121915-Female, pubmed-meshheading:17121915-Fibroblasts, pubmed-meshheading:17121915-Humans, pubmed-meshheading:17121915-Insulin-Like Growth Factor Binding Protein 3, pubmed-meshheading:17121915-Lung Neoplasms, pubmed-meshheading:17121915-Matrix Metalloproteinase 2, pubmed-meshheading:17121915-Mice, pubmed-meshheading:17121915-Mice, Nude, pubmed-meshheading:17121915-NIH 3T3 Cells, pubmed-meshheading:17121915-Neoplasm Metastasis, pubmed-meshheading:17121915-Receptor, IGF Type 1, pubmed-meshheading:17121915-Recombinant Proteins, pubmed-meshheading:17121915-Signal Transduction, pubmed-meshheading:17121915-Urokinase-Type Plasminogen Activator
pubmed:year
2006
pubmed:articleTitle
Antimetastatic activity of insulin-like growth factor binding protein-3 in lung cancer is mediated by insulin-like growth factor-independent urokinase-type plasminogen activator inhibition.
pubmed:affiliation
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Unit 432, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural