Desmopressin inhibits lung and lymph node metastasis in a mouse mammary carcinoma model of surgical manipulation

Background and Objectives: Desmopressin (DDAVP) is a synthetic derivative of vasopressin with hemostatic and fibrinolytic properties that has been used during surgery in patients with bleeding disorders. Our aim was to investigate the effect of DDAVP on lung and lymph node metastatic cell colonization using a preclinical mouse mammary carcinoma model of subcutaneous tumor manipulation and surgical excision. Methods: Female BALB/c mice bearing the highly aggressive F3II mammary carcinoma were subjected to repeated manipulations of primary tumors (0.5 kg/cm(2) during 2 min), followed (or not) by surgical excision. DDAVP was administered intravenously 30 min before and 24 h after each manipulation or surgery, at a dose of 2 mug/kg. At the end of the experiment, mice were sacrificed and necropsied. Results: Tumor manipulation induced dissemination to the axillary nodes and increased up to 6-fold the number of metastatic lung nodules. Perioperative treatment with DDAVP dramatically reduced regional metastasis. The incidence of lymph node involvement in manipulated animals was 12% with DDAVP and 87% without treatment (P < 0.02). Histopathological analysis of axillary nodes from DDAVP-treated animals showed sinusal histiocytosis and no evidence of cancer cells. Metastatic lung nodules were also reduced about 65% in animals treated with DDAVP (P = 0.026). Conclusions: Our results suggest a potential clinical application of DDAVP in the management of breast cancer, as well as other aggressive solid tumors. DDAVP may be useful to reduce the risk of metastatic cell colonization both during and after surgical manipulation. (C) 2002 Wiley-Liss, Inc.