title: Knockdown of TFPI-2 promotes migration and invasion of glioma cells.
abstract: 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.
authors.affiliation: Experimental Neurosurgery, Goethe-University Hospital, Frankfurt, Germany. f.gessler@med.uni-frankfurt.de
authors.forename: Florian
authors.initials: F
authors.lastname: Gessler
authors.forename: Valerie
authors.initials: V
authors.lastname: Voss
authors.forename: Volker
authors.initials: V
authors.lastname: Seifert
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Gerlach
authors.forename: Donat
authors.initials: D
authors.lastname: Kögel
mesh_terms: D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics* / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D006023:Glycoproteins; C021240:tissue-factor-pathway inhibitor 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1