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Antimetastatic effect of desmopressin in a mouse mammary tumor model

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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 μg/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.

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References

  1. Fidler IJ: Cancer metastasis. Br Med Bull 47: 157–177, 1991

    Google Scholar 

  2. Constantini V, Zacharski LR: The role of fibrin in tumor metastasis. Cancer Metastasis Rev 11: 283–290, 1992

    Google Scholar 

  3. Weiss L, Orr FW, Honn KV: Interactions of cancer cells with the microvasculature during metastasis. FASEB J 2: 12–21, 1988

    Google Scholar 

  4. Alonso DF, Skilton G, Farina HG, De Lorenzo MS, Gomez DE: Modulation of growth and urokinase secretion by vasopressin and closely related nonapeptides in metastatic mouse mammary tumor cells. Int J Oncol 10: 375–379, 1997

    Google Scholar 

  5. Mignatti P, Rifkin DB: Biology and biochemistry of proteinases in tumor invasion. Physiol Rev 73: 161–195, 1993

    Google Scholar 

  6. Richardson DW, Robinson AG: Desmopressin. Ann Intern Med 103: 228–239, 1985

    Google Scholar 

  7. Alonso DF, Farías EF, Urtreger A, Ladeda V, Vidal MC, Bal de Kier Joffé E: Characterization of F3II, a mammary sarcomatoid carcinoma cell line originated from a mouse adenocarcinoma. J Surg Oncol 62: 288–297, 1996

    Google Scholar 

  8. Urtreger A, Ladeda V, Puricelli L, Rivelli A, Vidal MC, Sacerdote de Lustig E, Bal de Kier Joffé E: Modulation of fibronectin expression and proteolytic activity associated with the invasive and metastatic phenotype in two new murine mammary tumor cell lines. Int J Oncol 11: 489–496, 1997

    Google Scholar 

  9. Alonso DF, Farías EF, Ladeda V, Davel L, Puricelli P, Bal de Kier Joffé E: Effects of synthetic urokinase inhibitors on local invasion and metastatic dissemination in a murine mammary tumor model. Breast Cancer Res Treat 40: 209–233, 1996

    Google Scholar 

  10. Inohara H, Akahami S, Koths K, Raz A: Interactions between galectin-3 and Mac-2-binding protein mediate cell-cell adhesion. Cancer Res 56: 4530–4534, 1996

    Google Scholar 

  11. Esumi N, Fan D, Fidler IJ: Inhibition of murine melanoma experimental metastasis by recombinant desulfatohirudine, a highly specific thrombin inhibitor. Cancer Res 51: 4549–4556, 1991

    Google Scholar 

  12. Gunji Y, Gorelik E: Role of fibrin coagulation in protection of murine tumor cells from destruction by cytotoxic cells. Cancer Res 48: 5216–5221, 1998

    Google Scholar 

  13. Alonso DF, Bertolesi GE, Farías EF, Gomez DE, Bal de Kier Joffé E: Inhibition of fibrinolysis by a synthetic urokinase inhibitor enhances lung colonization of metastatic murine mammary tumor cells. Oncol Rep 3: 1055–1058, 1996

    Google Scholar 

  14. Gader AMA, Da Costa J, Cash JD: A new vasopressin analogue and fibrinolysis. Lancet ii: 1417–1418, 1973

    Google Scholar 

  15. Mannucci PM, Aberg M, Nilsson IM, Robertson B: Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs. Br J Haematol 30: 81–93, 1975

    Google Scholar 

  16. Kanwar S, Woodman RC, Poon MC, Murohara T, Lefer AM, Davenpeck KL, Kubes P: Desmopressin induces endothelial P-selectin expression and leukocyte rolling in postcapillary venules. Blood 86: 2760–2766, 1995

    Google Scholar 

  17. Wun T, Paglieroni TG, Lachant NA: Desmopressin stimulates the expression of P-selectin on human platelets in vitro. J Lab Clin Med 126: 401–409, 1995

    Google Scholar 

  18. Yamada Y, Nakayama M, Nakano H, Mimura N, Yoshida S: Endothelium-dependent vasorelaxation evoked by desmopressin and involvement of nitric oxide in rat aorta. Am J Physiol 264: E203–E207, 1993

    Google Scholar 

  19. Hirano S: In vitro and in vivo cytotoxic effects of nitric oxide on metastatic cells. Cancer Lett 115: 57–62, 1997

    Google Scholar 

  20. Mannucci PM: Desmopressin: a nontransfusional form of treatment for congenital and acquired bleeding disorders. Blood 72: 1449–1455, 1988

    Google Scholar 

  21. Horrow JC: Desmopressin and antifibrinolytics. Int Anesthesiol Clin 28: 230–236, 1990

    Google Scholar 

  22. Lethagen S: Desmopressin (DDAVP) and hemostasis. Ann Hematol 69: 173–180, 1994

    Google Scholar 

  23. Brown DC, Purushotham AD, Birnie GD, George WD: Detection of intraoperative tumor cell dissemination in patients with breast cancer using reverse transcription and polymerase chain reaction. Surgery 117: 95–101, 1995

    Google Scholar 

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Alonso, D.F., Skilton, G., Farías, E.F. et al. Antimetastatic effect of desmopressin in a mouse mammary tumor model. Breast Cancer Res Treat 57, 271–275 (1999). https://doi.org/10.1023/A:1006291607871

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  • DOI: https://doi.org/10.1023/A:1006291607871

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