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.