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[Role of tissue factor pathway inhibitor-2 in ovarian tumor migration and invasion]
Ren Zhong1, Rui-Bin Huang, Shan-Jun Song
1Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, PR China. zhongren_7511@hotmail.com
Background & Objective:
Human tissue factor pathway inhibitor-2 (TFPI-2) is a newly discovered serine protease inhibitor, which inhibits plasmin, trypsin, matrix metalloproteinase (MMPs), but not urokinase, tissue-type plasminogen activators and thrombin. Earlier studies have shown that the production of TFPI-2 is downregulated during the progression of various cancers. The aim of this study was to elucidate the relationship between TFPI-2 expression and ovarian tumor migration and invasion.
Methods:
Human TFPI-2 expression vector pBos-Cite-neo/TFPI-2 was transfected into ovarian tumor cells line A2780. After the transfected cells were screened by G418, transfected and nontransfected cells were examined for TFPI-2 mRNA and protein by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. The number of transfected or nontransfected cells passing through membrane of Boyden chamber was counted as the basis assessing tumor cells migratory and invasive behaviors.
Results:
Expression of mRNA and protein of TFPI-2 were confirmed in transfected cells. In invasion assay, the number of TFPI-2-expressing cells to traverse a Matrigel-coated membrane was obviously decreased compared with that of nonexpressing cells (59.3+/-6.5 versus 109.7+/-5.5, P< 0.01); while in migration assay, no significant difference was observed between transfected and nontransfected cells (114.7+/-8.6 versus 127.3+/-7.1, P >0.05).
Conclusion:
Expression of TFPI-2 may strongly inhibit the invasive ability of ovarian tumor cells in vitro, but has no effect on the migratory ability, which provides an experimental basis for treating human ovarian tumor with gene therapy.
Insights
Tissue factor pathway inhibitor-2 (TFPI-2) significantly reduces ovarian tumor cell invasion but does not affect migration. This finding supports TFPI-2 as a potential target for ovarian cancer gene therapy.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Context:
- Tissue factor pathway inhibitor-2 (TFPI-2) is a serine protease inhibitor.
- TFPI-2 production is often reduced in various cancers.
- Ovarian tumors exhibit altered TFPI-2 expression levels.
Purpose:
- To investigate the role of TFPI-2 in ovarian tumor cell migration and invasion.
- To determine the relationship between TFPI-2 expression and ovarian cancer progression.
Summary:
- TFPI-2 was expressed in ovarian tumor cells using a vector transfection method.
- Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot confirmed TFPI-2 expression.
- Invasion assays showed significantly reduced cell traversal through a Matrigel-coated membrane in TFPI-2-expressing cells.
- Migration assays revealed no significant difference in cell movement between TFPI-2-expressing and non-expressing cells.
Impact:
- TFPI-2 expression inhibits ovarian tumor cell invasion in vitro.
- TFPI-2 does not influence ovarian tumor cell migration.
- These results provide a basis for exploring TFPI-2 gene therapy for ovarian cancer.
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