Antimetastatic effect of desmopressin in a mouse mammary tumor model

Abstract

We have investigated the effects of desmopressin (DDAVP), a synthetic analog of the natural hormone vasopressin, on experimental lung colonization of mammary tumor cells using a syngeneic BALB/c mouse model. Coinjection of DDAVP (1-2 microg/kg body weight) at the time of i.v. inoculation of F3II carcinoma cells or LM3 adenocarcinoma cells significantly inhibited the formation of experimental lung metastases. In both cases, the number of pulmonary nodules was reduced about 70%. Inhibition of metastasis was also obtained with i.v. administration of DDAVP 24 h after tumor cell inoculation. Interestingly, the inhibition of lung metastasis was not due to direct cytotoxic effects of DDAVP on mammary tumor cells. The in vitro formation of multicellular aggregates in the presence of citrated plasma from control and DDAVP-treated mice was also examined. Control plasma rapidly induced a significant tumor cell aggregation. In contrast, in the presence of plasma from DDAVP-treated mice, tumor cells remained as a single cell suspension. DDAVP may help to dissolve the protective fibrin shield of circulating tumor cells. Our data suggest, for the first time, that adjuvant DDAVP therapy may impair successful implantation of circulating mammary tumor cells.

Provasopressin expression by breast cancer cells: implications for growth and novel treatment strategies

“…Taylor et al demonstrated that the V2-specific agonist dDAVP did not inhibit AVP binding to Mcf7 cells [11], although later work has shown that these cells do express the V2 receptor [16]. dDAVP can have an anti-metastatic effect on breast cancer cells in mouse tumor models [18,38], however those studies indicate that dDAVP did not have a cytotoxic effect on the tumor cells. Additionally, human V1a receptor expressing CHO cells displayed increased thymidine uptake in response to AVP, while human V2 receptor expressing CHO cells displayed a reduction of thymidine uptake [60].…”

“…When Mcf7 and Skbr3 cells were cultured in the presence of 10 nM SR49059 alone, they displayed similar growth as untreated control cells (not shown). The V2 agonist dDAVP appears to inhibit breast cancer cell metastasis [18,38], and the V2 receptor may mediate anti-proliferative effects [17]. Cells were exposed to 10 nM dDAVP alone or in the presence of the V2 antagonist SR121463 and their proliferation was measured.…”

Canine Mammary Tumors: Risk Factors, Prognosis and Treatments

“…This peptide has hemostatic and antidiuretic effects, and has been used in the management of diabetes insipidus (Manucci, 1997). Interestingly, DDAVP inhibited experimental lung metastasis of mammary tumor cells in a mouse model (Alonso et al, 1999). In human breast cancer cell lines, DDAVP exhibits moderate antiproliferative effects (Iannucci et al, 2011).…”

A combination of desmopressin and docetaxel inhibit cell proliferation and invasion mediated by urokinase-type plasminogen activator (uPA) in human prostate cancer cells

“…Desmopressin is a safe and effective hemostatic agent in patients with von Willebrand disease, hemophilia A, and other bleeding disorders [4,5]. Recent reports suggest that desmopressin inhibits tumor progression and metastasis in in vivo models [6][7][8]. Although these studies suggest that desmopressin has both anti-tumor and anti-metastatic effects on cancer cells, the mechanism of action has not been determined.…”