title: Desmopressin reduces melanoma lung metastasis in transgenic mice overexpressing tissue inhibitor of metalloproteinases-1.
abstract: Desmopressin (DDAVP) is a synthetic vasopressin analog capable of inducing an increase in the plasma levels of von Willebrand factor and coagulation factor VIII. DDAVP has been used during surgery to prevent bleeding in patients with coagulation defects. We have previously demonstrated that adjuvant perioperative DDAVP therapy inhibits lung and lymph node metastasis in a breast cancer model. Here the effect of DDAVP on experimental lung colonization of B16 melanoma cells was investigated in a transgenic mice model with high levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) in the systemic circulation. Transgenic C57BL/6j-CBA mice overexpressing human TIMP-1 in the liver under the control of the mouse albumin promoter/enhancer were employed. Treatment with DDAVP (2 microg/kg/dose) at the time of intravenous injection of B16 cells significantly inhibited the formation of lung metastases in TIMP-1 transgenic animals (p = 0.021), while no significant effect was obtained in control hybrid mice. The inhibition was not due to direct cytotoxic effects of DDAVP on tumor cells and no expression of vasopressin receptors was detected in B16 cells. Our data indicate that DDAVP therapy may impair successful implantation of circulating melanoma cells and suggest that high levels of circulating TIMP-1 display a cooperative role in the antitumor activity of the compound.
authors.affiliation: Laboratory of Molecular Oncology, Department of Science and Technology, Quilmes National University, Bernal, Buenos Aires, Argentina.
authors.forename: Giselle V
authors.initials: GV
authors.lastname: Ripoll
authors.forename: Hernán G
authors.initials: HG
authors.lastname: Farina
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshiji
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Gomez
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Alonso
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000235:genetics; D006490:Hemostatics / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D017483:Receptors, Vasopressin / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*
chemical_list: D006490:Hemostatics; D017483:Receptors, Vasopressin; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D003894:Deamino Arginine Vasopressin