title: Beneficial role of overexpression of TFPI-2 on tumour progression in human small cell lung cancer.
abstract: Tissue factor pathway inhibitor-2 (TFPI-2) is a potent inhibitor of plasmin, a protease which is involved in tumour progression by activating (MMPs). This therefore makes TFPI-2 a potential inhibitor of invasiveness and the development of metastases. In this study, low levels of TFPI-2 expression were found in 65% of patients with small cell lung cancer (SCLC), the most aggressive type of lung cancer. To study the impact of TFPI-2 in tumour progression, TFPI-2 was overexpressed in NCI-H209 SCLC cells which were orthotopically implanted in nude mice. Investigations showed that TFPI-2 inhibited lung tumour growth. Such inhibition could be explained in vitro by a decrease in tumour cell viability, blockade of G1/S phase cell cycle transition and an increase in apoptosis shown in NCI-H209 cells expressing TFPI-2. We also demonstrated that TFPI-2 upregulation in NCI-H209 cells decreased MMP expression, particularly by downregulating MMP-1 and MMP-3. Moreover, TFPI-2 inhibited phosphorylation of the MAPK signalling pathway proteins involved in the induction of MMP transcripts, among which MMP-1 was predominant in SCLC tissues and was inversely expressed with TFPI-2 in 35% of cases. These results suggest that downregulation of TFPI-2 expression could favour the development of SCLC.
authors.affiliation: EA 6305, Université François Rabelais de Tours, Tours F-37032, France ; Centre d'Etude des Pathologies Respiratoires, UMR 1100/EA6305, Tours F-37032, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Lavergne
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Jourdan
authors.forename: Claire
authors.initials: C
authors.lastname: Blechet
authors.forename: Serge
authors.initials: S
authors.lastname: Guyetant
authors.forename: Alain Le
authors.initials: AL
authors.lastname: Pape
authors.forename: Nathalie
authors.initials: N
authors.lastname: Heuze-Vourc'h
authors.forename: Yves
authors.initials: Y
authors.lastname: Courty
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lerondel
authors.forename: Julien
authors.initials: J
authors.lastname: Sobilo
authors.forename: Sophie
authors.initials: S
authors.lastname: Iochmann
authors.forename: Pascale
authors.initials: P
authors.lastname: Reverdiau
keywords: Metalloproteases; Mouse orthotopic model; Small cell lung cancer; Tissue factor pathway inhibitor-2
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