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Time and dose dependency of the suppression of pulmonary metastases of rat mammary cancer by amiloride

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Abstract

Amiloride is an inhibitor of urokinase plasminogen activator (uPA), an essential component of the plasminogen/plasmin enzyme system. Inhibition of uPA prevents the conversion of plasminogen to tumor cell surface bound plasmin which is required for initiation of the metastatic process. MATB rat mammary cancer cells were introduced into the jugular venous system of 80 Fisher 344 female rats. Amiloride at high and low dosages was administered in the drinking water at the time of, prior to or several days following the tumor cell inoculation and continued daily for 10 days post inoculation. Control rats were maintained on water alone. The middle lobe of the right lung was examined microscopically for numbers of metastases. Suppression of metastases was significant at high amiloride dosages in all groups, and at low dosage when administered prior to inoculation. We conclude that amiloride suppresses induced metastases of rat mammary cancer, the effect being dose- and time-dependent. © Rapid Science Ltd.

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References

  1. Flamigni C, Bulletti C, Polli V, et al.1991, Factors regulating interaction between trophoblast and human endometrium. Ann NY Acad Sci, 622, 176-90.

    Google Scholar 

  2. Blasi F, 1993, Urokinase and urokinase receptor: a paracrine/autocrine system regulating cell migration and invasiveness. BioEssays, 15, 105-11.

    Google Scholar 

  3. Malone JM, Wangensteen SL, Moore WS and Keown K, 1979, The fibrinolytic system: a key to tumor metastasis? Ann Surg, 190, 342-9.

    Google Scholar 

  4. Dano K, Andreasen PA, Grondahl-Hansen J, et al.1985, Plasminogen activators, tissue degradation and cancer. Adv Cancer Res, 44, 139-266.

    Google Scholar 

  5. Mignatti P, Robbins E and Rifkin DB, 1986, Tumor invasion through the human amniotic membrane: requirement for a proteinase cascade. Cell, 47, 487-98.

    Google Scholar 

  6. Terranove VP, Maslow D and Markus G, 1989, Directed migration of murine and human tumor cells to collagenases and other proteases. Cancer Res, 49, 4835-1.

    Google Scholar 

  7. Wong RS and Passaro E, 1989, Growth factors, oncogenesis and the autocrine hypothesis. Surg Gynecol Obstet, 160, 468-73.

    Google Scholar 

  8. Ng R, Kellen JA and Wong CHW, 1983, Plasminogen activators as markers of tumor colonization potential. Inv Met, 3, 243-8.

    Google Scholar 

  9. Ossowski L, Clunie G, Masucci MT and Blasi F, 1991, In vivoparacrine interaction between urokinase and its receptor: effect on tumor cell invasion. J Cell Biol, 107, 1107-12.

    Google Scholar 

  10. Ossowski L, 1988, In vivoinvasion of modified chorioallantoic membrane by tumor cells: the role of surface-bound urokinase. J Cell Biol, 107, 2437-45.

    Google Scholar 

  11. Rabbani SA, Harakadis P, Davidson DJ, et al.1995, Prevention of prostate cancer metastasis in vivoby a novel synthetic inhibitor of urokinase-type plasminogen activator (uPA). Int J Cancer, 63, 840-5.

    Google Scholar 

  12. Ossowski R and Reich E, 1983, Antibodies to plasminogen activator inhibit human tumor metastasis. Cell, 35, 611-19.

    Google Scholar 

  13. Crowley CW, Cohen RL, Lucas BK, et al.1993, Prevention of metastasis by inhibition of the urokinase receptor. Cell Biol, 90, 5021-5.

    Google Scholar 

  14. Kellen JA, Mirakian A and Kolin A, 1988, Antimetastatic effect of amiloride in an animal tumor model. Anticancer Res, 8, 1373-6.

    Google Scholar 

  15. Evans DM and Lin PL, 1995, Suppression of pulmonary metastases of rat mammary cancer by recombinant urokinase plasminogen activator inhibitor. The Am Surg, 8, 692-7.

    Google Scholar 

  16. Baker MS, Bleakley P, Woodrow G and Doe WF, 1990, Inhibition of cancer cell urokinase plasminogen activator by its specific inhibitor PAI-2 and subsequent effects on extracellular matrix degeneration. Cancer Res, 50, 4676-84.

    Google Scholar 

  17. Koo JY, Parekh D, Townsend CM, et al.1992, Amiloride inhibits the growth of human colon cancer cells in vitro. Surg Oncol, 1, 385-9.

    Google Scholar 

  18. Vassalli JD and Belin D, 1987, Amiloride selectively inhibits the urokinase-type plasminogen activator. Febs Lett, 214, 187-91.

    Google Scholar 

  19. Alliegro MC, Alliegro MA, Cragoe EJ and Glaser BM, 1993, Amiloride inhibition of angiogenesis in vitro. J Exp Zool, 267, 245-52.

    Google Scholar 

  20. Avery RL, Connor TB and Farazdaghi M, 1990, Systemic amiloride inhibits experimentally induced neovascularization. Arch Ophth, 108, 1474-6.

    Google Scholar 

  21. Benos DJ, 1982, Amiloride: A molecular probe of sodium transport in tissues and cells. Am J Physiol, 242, 131-45.

    Google Scholar 

  22. Ulrich-Baker MG, Wang P, Fitzpatrick L and Johnson LR, 1988, Amiloride inhibits rat mucosal ODC activity and DNA synthesis. Am J Physiol, 254, 405-15.

    Google Scholar 

  23. Riley JH and Cornelius LM, 1989, Electrolytes, blood gasses and acid base balance. In: Loeb WF and Quimby FW, eds. The Clinical Chemistry of Laboratory Animals.Oxford: Pergamon Press, pp. 345-406.

    Google Scholar 

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Evans, D.M., Sloan-Stakleff, K., Arvan, M. et al. Time and dose dependency of the suppression of pulmonary metastases of rat mammary cancer by amiloride. Clin Exp Metastasis 16, 353–357 (1998). https://doi.org/10.1023/A:1006517614491

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  • DOI: https://doi.org/10.1023/A:1006517614491

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