Abstract | BACKGROUND:
Tissue factor (TF) pathway inhibitor-1 ( TFPI) is expressed in several malignant tissues- and cell lines and we recently reported that it possesses anti- tumor effects in breast cancer cells, indicating a biological role of TFPI in cancer. The two main splice variants of TFPI; TFPIα and TFPIβ, are both able to inhibit TF- factor VIIa (FVIIa) activity in normal cells, but only TFPIα circulates in plasma. The functional importance of TFPIβ is therefore largely unknown, especially in cancer cells. We aimed to characterize the expression and function of TFPIα, TFPIβ, and TF in a panel of tumor derived breast cancer cell lines in comparison to normal endothelial cells. METHODS: RESULTS: The expression of both isoforms of TFPI varied considerably among the breast cancer cell lines tested, from no expression in Sum149 cells to levels above or in the same range as normal endothelial cells in Sum102 and MDA-MB-231 cells. PI-PLC treatment released both TFPIα and TFPIβ from the breast cancer cell membrane and increased TF activity on the cell surface, showing TF-FVIIa inhibitory activity of the glycosylphosphatidylinositol- (GPI-) anchored TFPI. Heparin treatment released TFPIα without decreasing the cell surface levels, thus indicating the presence of intracellular storage pools of TFPIα in the breast cancer cells. CONCLUSION: GPI-attached TFPI located at the surface of breast cancer cells inhibited TF activity and could possibly reduce TF signaling and breast cancer cell growth locally, indicating a therapeutic potential of the TFPIβ isoform.
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Authors | Benedicte Stavik, Mari Tinholt, Marit Sletten, Grethe Skretting, Per Morten Sandset, Nina Iversen |
Journal | Journal of hematology & oncology
(J Hematol Oncol)
Vol. 6
Pg. 5
(Jan 15 2013)
ISSN: 1756-8722 [Electronic] England |
PMID | 23320987
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Lipoproteins
- Protein Isoforms
- RNA, Messenger
- lipoprotein-associated coagulation inhibitor
- Thromboplastin
- Factor VIIa
- Factor Xa
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Topics |
- Blotting, Western
- Breast Neoplasms
(metabolism, pathology)
- Cell Membrane
(metabolism)
- Cells, Cultured
- Endothelium, Vascular
(cytology, metabolism)
- Enzyme-Linked Immunosorbent Assay
- Factor VIIa
(antagonists & inhibitors, metabolism)
- Factor Xa
(metabolism)
- Female
- Flow Cytometry
- Fluorescent Antibody Technique
- Humans
- Lipoproteins
(metabolism)
- Protein Isoforms
- RNA, Messenger
(genetics)
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- Thromboplastin
(metabolism)
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