title: Ex vivo and in vivo delivery of anti-tissue factor short interfering RNA inhibits mouse pulmonary metastasis of B16 melanoma cells.
abstract: OBJECTIVE
  The coagulation trigger tissue factor has been implicated in tumor growth, angiogenesis, and metastasis. In this study, we explore the effects of ex vivo and in vivo delivery of short interfering RNA (siRNA) targeting tissue factor on B16 melanoma colonization of the lung in a murine model for metastasis. The purposes of this work are to establish a noncytotoxic in vivo model for investigation of tissue factor function and provide preclinical assessment of the therapeutic potential of tissue factor siRNA for prevention of metastasis.
  
  
  RESULTS
  C57BL/6 mice were evaluated for pulmonary metastases following tail vein injection of B16 cells transfected with either active or inactive siRNA. Mice receiving cells transfected with active siRNA had significantly lower numbers of pulmonary tumors compared with mice injected with control cells (transfected with inactive siRNA). The average time point at which the mice started to exhibit tumor-associated stress was also increased significantly from 22 days for the control group to 27 days for the experimental group (P = 0.01). In a therapeutically more relevant model, where the siRNA was delivered i.p. and the cells (untransfected) by tail vein injection, an inhibitory effect on metastasis was observed when the siRNA treatment was initiated either before or at the time of cell injection.
  
  
  CONCLUSIONS
  The results suggest that tissue factor has a crucial function in promoting lung tumor metastasis of blood-borne tumor cells in the early stages of the tumor take process and further suggest that treatment with tissue factor siRNA may become a viable clinical strategy for prevention of tumor metastasis.
authors.affiliation: The Biotechnology Centre of Oslo, Norway.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Amarzguioui
authors.forename: Qian
authors.initials: Q
authors.lastname: Peng
authors.forename: Merete T
authors.initials: MT
authors.lastname: Wiiger
authors.forename: Vlada
authors.initials: V
authors.lastname: Vasovic
authors.forename: Eshrat
authors.initials: E
authors.lastname: Babaie
authors.forename: Torgeir
authors.initials: T
authors.lastname: Holen
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.forename: Hans
authors.initials: H
authors.lastname: Prydz
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D013925:Thromboplastin / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D013925:Thromboplastin