Document Detail

TFPI-2 silencing increases tumour progression and promotes metalloproteinase 1 and 3 induction through tumour-stromal cell interactions.
MedLine Citation:
PMID:  20015200     Owner:  NLM     Status:  In-Data-Review    
Tissue factor pathway inhibitor-2 (TFPI-2) is a potent inhibitor of plasmin which activates matrix metalloproteinases (MMPs) involved in degradation of the extracellular matrix. Its secretion in the tumour microenvironment makes TFPI-2 a potential inhibitor of tumour invasion and metastasis. As demonstrated in aggressive cancers, TFPI-2 is frequently down-regulated in cancer cells, but the mechanisms involved in the inhibition of tumour progression remained unclear. We showed in this study that stable TFPI-2 down-regulation in the National Cancer Institute (NCI)-H460 non-small cell lung cancer cell line using specific micro interfering micro-interfering RNA promoted tumour progression in a nude mice orthotopic model that resulted in an increase in cell invasion. Moreover, TFPI-2 down-regulation enhanced cell adhesion to collagen IV and laminin via an increase in α(1) integrin on cell surface, and increased MMP expression (mainly MMP-1 and -3) contributing to cancer cell invasion through basement membrane components. This study also reveals for the first time that pulmonary fibroblasts incubated with conditioned media from TFPI-2 silencing cancer cells exhibited increased expression of MMPs, particularly MMP-1, -3 and -7, that are likely involved in lung cancer cell invasion through the surrounding stromal tissue, thus enhancing formation of metastases.
Guillaume Gaud; Sophie Iochmann; Audrey Guillon-Munos; Benjamin Brillet; Stéphanie Petiot; Florian Seigneuret; Antoine Touzé; Nathalie Heuzé-Vourc'h; Yves Courty; Stéphanie Lerondel; Yves Gruel; Pascale Reverdiau
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cellular and molecular medicine     Volume:  15     ISSN:  1582-4934     ISO Abbreviation:  J. Cell. Mol. Med.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-10-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101083777     Medline TA:  J Cell Mol Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  196-208     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Inserm, U618, Université François Rabelais, Tours, France TAAM-UPS44, CIPA, CNRS d'Orléans, Orléans, France Service d'Hématologie-Hémostase, CHRU Trousseau, Tours, France.
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