Document Detail


Transient RNA silencing of tissue factor pathway inhibitor-2 modulates lung cancer cell invasion.
MedLine Citation:
PMID:  19267203     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tissue Factor Pathway Inhibitor-2 (TFPI-2) is a potent inhibitor of plasmin which activates metalloproteinases (MMPs) involved in extracellular matrix (ECM) degradation. Its secretion in ECM makes TFPI-2 a potential inhibitor to regulate tumour invasion and metastasis. Moreover, TFPI-2 is frequently downregulated, particularly in aggressive cancers. In this study, we silenced TFPI-2 in the NCI-H460 non-small cell lung cancer cell line and evaluated the role of TFPI-2 in cell invasion and its impact on MMPs expression. As the effects of siRNA are transient, the consequences of both gene silencing and restoration to normal expression could be studied kinetically in the same cells. We showed that TFPI-2 expression by NCI-H460 cells was effectively downregulated using specific small interfering RNA and this silencing was associated with an increase in the invasive potential of tumour cells while migration was not affected. We also showed that mRNA levels and protein expression of MMP-2, -3, -9, -14 were not influenced by TFPI-2 silencing. Moreover, the gelatinase activity of MMP-2 and MMP-9 was unmodified. In contrast, MMP-1 mRNA levels and protein were significantly and similarly increased in cells transfected with TFPI-2 siRNA. In conclusion, this study confirms that TFPI-2 downregulation can contribute to tumour invasion of lung cancer cells.
Authors:
Sophie Iochmann; Claire Bléchet; Valérie Chabot; Annabelle Saulnier; Aniça Amini; Guillaume Gaud; Yves Gruel; Pascale Reverdiau
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-07
Journal Detail:
Title:  Clinical & experimental metastasis     Volume:  26     ISSN:  1573-7276     ISO Abbreviation:  Clin. Exp. Metastasis     Publication Date:  2009  
Date Detail:
Created Date:  2009-05-20     Completed Date:  2009-06-11     Revised Date:  2010-07-08    
Medline Journal Info:
Nlm Unique ID:  8409970     Medline TA:  Clin Exp Metastasis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  457-67     Citation Subset:  IM    
Affiliation:
Inserm U618, Protéases et Vectorisation Pulmonaires, Faculté de Médecine, Université François Rabelais, IFR 135, 10 Boulevard Tonnellé, 37032, Tours Cedex, France. iochmann@med.univ-tours.fr
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Non-Small-Cell Lung / metabolism*,  pathology
Cell Line, Tumor
Cell Movement
Down-Regulation
Extracellular Matrix / metabolism
Gene Expression Regulation, Neoplastic*
Gene Silencing*
Glycoproteins / metabolism*
Humans
Lung Neoplasms / metabolism*,  pathology
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / metabolism
Neoplasm Invasiveness
RNA / metabolism*
RNA, Small Interfering / metabolism
Chemical
Reg. No./Substance:
0/Glycoproteins; 0/RNA, Small Interfering; 0/tissue-factor-pathway inhibitor 2; 63231-63-0/RNA; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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