Tissue factor enhances protease-activated receptor-2-mediated factor VIIa cell proliferative properties

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Biology

Background:

• Factor VIIa (FVIIa) possesses cell proliferative properties beyond hemostasis, implicated in angiogenesis and tumor growth.
• The roles of tissue factor (TF) and protease-activated receptors (PARs) in FVIIa-mediated cell proliferation require clarification.

Purpose of the Study:

• To investigate the hypothesis that FVIIa induces cell proliferation via a mechanism involving TF and PAR-2.

Main Methods:

• Utilized human recombinant FVIIa on BOSC23 cells expressing human TF.
• Employed a reporter gene assay with the DNA primase 1 (PRIM1) promoter linked to chloramphenicol acetyl transferase (CAT).
• Assessed the effects of TF antisense oligonucleotides, PAR-1, and PAR-2 antagonists, intracellular calcium, and p44/42 MAP kinase phosphorylation.

Main Results:

• FVIIa dose-dependently increased cell proliferation and PRIM1 induction, potentiated by TF and abrogated by TF antisense.
• PRIM1 induction by FVIIa was abolished by PAR-2 but not PAR-1 antagonists.
• FVIIa's proliferative effects involved TF-dependent intracellular calcium increase and p44/42 MAP kinase phosphorylation.

Conclusions:

• FVIIa induces PRIM1 and cell proliferation through a TF- and PAR-2-dependent pathway.
• Thrombin's proliferative effects are PAR-1-dependent and TF-independent.
• Inhibitors targeting the FVIIa-TF-PAR-2 pathway may suppress cell proliferation.