title: Soluble tissue factor induces coagulation on tumor endothelial cells in vivo if coadministered with low-dose lipopolysaccharides.
abstract: OBJECTIVE
  This study was performed to evaluate the mechanisms leading to tumor vessel occlusion by tissue factor-based drugs, which are used in vascular targeting approaches for the treatment of malignant tumors.
  
  
  RESULTS
  The effects of nontargeted soluble tissue factor were evaluated in vitro and in vivo. Tumor-bearing mice were treated with (1) the extracellular portion of tissue factor (soluble tissue factor), (2) low nontoxic doses of lipopolysaccharides, or (3) a combination thereof. The combination treatment showed the best effects and resulted in selective thrombosis of tumor vessels. On the basis of our data from subsequent in vitro analyses, including surface plasmon resonance measurements and endothelial cell based coagulation assays, we propose a model on how soluble tissue factor, although lacking its membrane anchor, can promote selective tumor vessel occlusion.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report to describe the molecular mechanisms of coagulation induction by untargeted soluble tissue factor in vivo. Combination treatments including soluble tissue factor might represent an alternative vascular targeting approach for the treatment of malignant tumors.
authors.affiliation: Department of Internal Medicine I, University Hospital Cologne, Cologne, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Philipp
authors.forename: Ariane
authors.initials: A
authors.lastname: Dienst
authors.forename: Maike
authors.initials: M
authors.lastname: Unruh
authors.forename: Anke
authors.initials: A
authors.lastname: Wagener
authors.forename: Andrea
authors.initials: A
authors.lastname: Grunow
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
authors.forename: Jochen W U
authors.initials: JW
authors.lastname: Fries
authors.forename: Claudia
authors.initials: C
authors.lastname: Gottstein
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004621:Embolization, Therapeutic / Q000379:methods*; D004789:Enzyme Activation / Q000187:drug effects; D015951:Factor Xa / Q000096:biosynthesis; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012995:Solubility; D020349:Surface Plasmon Resonance; D018243:Teratocarcinoma / Q000098:blood supply / Q000628:therapy*; D013925:Thromboplastin / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D008070:Lipopolysaccharides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C482199:lipopolysaccharide, E coli O55-B5; D013925:Thromboplastin; D015951:Factor Xa