TFPI-2 silencing increases tumour progression and promotes metalloproteinase 1 and 3 induction through tumour-stromal cell interactions.
Bottom Line: 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.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.
Affiliation: Inserm, U618, Université François Rabelais, Tours, France.Show MeSH
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Mentions: To determine whether various signalling pathways were activated in TFPI-2 down-regulated non-small lung cancer cells, we measured the activities of 10 signal transduction pathways involved in cancer biology using a dual-luciferase reporter assay. As shown in Fig. 6, an increase in relative luciferase activity was observed for extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK) and NF-κB pathways in NCI-H460 clones when compared to negative control. In addition, down-regulation of TFPI-2 in miRNA-1b and -2b clones was also associated with a slight increase in NF-κB pathway (P > 0.05) and a significant increase in the ERK and JNK pathways compared to the miRNA-Neg clone (P < 0.05). Other signalling pathway activities remained unchanged in all NCI-H460 clones compared to negative control.
Affiliation: Inserm, U618, Université François Rabelais, Tours, France.