title: Leptin upregulates tissue factor expression in human breast cancer MCF-7 cells.
abstract: BACKGROUND
  Obesity is a risk factor for both cardiovascular disease and cancer development. Leptin, a cytokine produced by adipose tissue, controls different processes in peripheral tissues, including cancer development and thrombotic disorders in patients with a variety of clinical disorders. Tissue factor (TF), the trigger of blood clotting, is abundant in the adipose tissue. 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.
  
  
  METHODS
  MCF-7 cells were incubated with or without the different reagents at 37 °C. At the end of incubation, cells were tested for procoagulant activity by a one-stage clotting assay, TF and TNF-α antigen levels and mRNA by ELISA and real-time RT-PCR, respectively. Leptin receptor was studied by FACS.
  
  
  RESULTS
  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-α mRNA synthesis and secretion from MCF7. An anti-TNF-α MoAb completely abolished the leptin-induced TF expression.
  
  
  CONCLUSIONS
  These data support the hypothesis that leptin, by its upregulation of TF, possibly mediated by TNF-α synthesis, may contribute to processes underlying both cancer and vascular cell disorders.
authors.affiliation: Research Laboratories, Giovanni Paolo II Center for High Technology Research, and Education in Biomedical Sciences, Catholic University, Largo Gemelli 1, 86100 Campobasso, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Napoleone
authors.forename: Antonella
authors.initials: A
authors.lastname: Cutrone
authors.forename: Daniela
authors.initials: D
authors.lastname: Cugino
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Latella
authors.forename: Filomena
authors.initials: F
authors.lastname: Zurlo
authors.forename: Licia
authors.initials: L
authors.lastname: Iacoviello
authors.forename: Giovanni
authors.initials: G
authors.lastname: de Gaetano
authors.forename: Maria Benedetta
authors.initials: MB
authors.lastname: Donati
authors.forename: Roberto
authors.initials: R
authors.lastname: Lorenzet
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D013925:Thromboplastin