Glioblastoma is the most malignant
primary brain tumor. Due to its highly promigratory and proinvasive properties, standard
therapy including surgery,
chemotherapy and radiation fails in eradicating this highly aggressive type of
cancer. Here, we evaluated the role of
TFPI-2, a Kunitz-type
serine protease inhibitor, which has been previously described as a tumor suppressor gene in several types of
cancer, including
glioma.
TFPI-2 expression was absent in five of nine investigated high-grade
glioma cell lines. Lentiviral knockdown of
TFPI-2 in two of the TFPI-2-expressing cell lines (MZ-18 and Hs 638) was associated with pronounced changes in the cellular behavior:
glioma cell proliferation, migration and invasion were significantly increased in
TFPI-2 knockdown cells in comparison to empty vector-transfected control cells. Since
TFPI-2 might exert its
tumor suppressor function by inhibiting
MMPs, we subsequently analyzed the effects of specific
MMP inhibitors on cell invasion of
TFPI-2 KD cells vs. control cells. The data obtained from these experiments suggest that the anti-invasive properties of
TFPI-2 are associated with inhibition of MMP-1 and MMP-2, while inhibition of MMP-9 seems to play a minor role in this context. Our findings underscore the important role of
TFPI-2 as a tumor suppressor gene and indicate that
TFPI-2 may be a useful diagnostic marker for the aggressive phenotype of glial
tumors.