Since TF, often expressed by cancer cells, is considered a hallmark of cancer progression, we investigated whether leptin could modulate TF in the human metastatic breast carcinoma cell line MCF-7.
MCF-7 cells were incubated with or without the different reagents at 37 掳C. At the end of incubation, cells were tested for procoagulant activity by a one-stage clotting assay, TF and TNF-伪 antigen levels and mRNA by ELISA and real-time RT-PCR, respectively. Leptin receptor was studied by FACS.
Both TF activity and antigen constitutively expressed by MCF-7 were significantly increased by leptin in a dose-dependent fashion. TF mRNA levels were also enhanced indicating that leptin exerts its effect at the transcription level. The effect of leptin was specific and required binding to its receptor (Ob-R), which was found on the surface of the cells, since antibodies against leptin and Ob-R completely prevented TF expression upregulation.
In addition, leptin enhanced both TNF-伪 mRNA synthesis and secretion from MCF7. An anti-TNF-伪 MoAb completely abolished the leptin-induced TF expression.
These data support the hypothesis that leptin, by its upregulation of TF, possibly mediated by TNF-伪 synthesis, may contribute to processes underlying both cancer and vascular cell disorders.