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Tissue factor pathway inhibitor‐2 suppresses the production of active matrix metalloproteinase‐2 and is down‐regulated in cells harboring activated ras oncogenes
Author(s) -
Izumi Hideki,
Takahashi Chiaki,
Oh Junseo,
Noda Makoto
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01902-5
Subject(s) - chemistry , matrix metalloproteinase , microbiology and biotechnology , matrix (chemical analysis) , cancer research , biochemistry , biology , chromatography
A human placenta cDNA expression library was screened for genes inducing flat reversion when transfected into a v‐K‐ras ‐transformed NIH3T3 cell line, DT. One such gene was found to encode a Kunitz‐type serine protease inhibitor, tissue factor pathway inhibitor‐2 (TFPI‐2). While the TFPI‐2 mRNA can be detected in normal human fibroblasts (MRC‐5), it is down‐regulated in MRC‐5 cells expressing an activated H‐ras oncogene and in the human fibrosarcoma cell line, HT1080. Restored expression of the TFPI‐2 gene in HT1080 cells resulted in the suppression of matrix invasion activity in vitro with concomitant decrease in the relative amount of active matrix metalloproteinase‐2 secreted from the cells. When DT cells were cultured in the presence of conditioned medium and extracellular matrix prepared from TFPI‐2 ‐transfected HT1080 cells, increased attachment and flat reversion were observed. These results suggest that TFPI‐2 may be required for the maintenance of the integrity of extracellular matrix in normal tissues and its down‐regulation as a result of oncogene activation may contribute to the malignant phenotypes of tumor cells.