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Clinical & Experimental Metastasis

, Volume 15, Issue 4, pp 393–399 | Cite as

Influence of antiestrogens on the migration of breast cancer cells using an in vitro wound model

  • Annie C. Mathew
  • Talitha T. Rajah
  • Gina M. Hurt
  • S. M. Abbas Abidi
  • John J. Dmytryk
  • J. Thomas Pento
Article

Abstract

The metastasis of malignant tumor cells to other organs in the body is the major cause of cancer-related patient mortality. Therefore, the inhibition of tumor cell motility is critical in the prevention or control of tumor malignancy. In the present study, the antimetastatic potential of antiestrogens [tamoxifen (TAM); ICI-182,780 (ICI); and Analog II (AII)] on highly invasive, estrogen receptor (ER)-negative MDA-MB-231 (MDA) and non-invasive, ER-positive MCF-7 (MCF) human breast cancer cell lines was investigated using an in vitro wound model. Wounds were created in confluent cell cultures and repopulation of the wound space was evaluated by counting the number of cells that migrated into the wound area and by measuring the maximum distance traveled. In addition, the number of cells that were passively seeded into the wounded area was determined. ICI and AII reduced the number of MCF cells that migrated into the wounded area and reduced the number of viable passively seeded MDA cells. Unlike ICI and AII, TAM appeared to enhance MCF and MDA cell movement. This study indicates that the in vitro wound technique is applicable to the study of breast cancer cell movement in response to antiestrogens and other antimetastatic agents. It also demonstrates that antiestrogens differ in their influence on breast cancer cell migration.

antiestrogens breast cancer cells cell migration in vitro wounding 

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References

  1. 1.
    Nicolson GL, 1988, Cancer metastasis-tumor cell and host organ properties important in colonization of specific secondary sites. Biochem Biophys Acta, 948, 175–224.Google Scholar
  2. 2.
    Dvorak HF, 1986, Tumors: wounds that do not heal. New Engl J Med, 315, 1650–9.Google Scholar
  3. 3.
    Jordan VC, 1993, A current view of tamoxifen for the treatment and prevention of breast cancer. Br J Pharmacol, 110, 507–17.Google Scholar
  4. 4.
    Clarke R, Thompson EW, Leonessa F, Lippman J, Frandsen TL and Brunner N, 1993, Hormone resistance, invasiveness, and metastatic potential in breast cancer. Breast Cancer Res Treat, 24, 227–39.Google Scholar
  5. 5.
    Leonessa F, Boulay V, Wright A, Thompson EW, Brunner N and Clarke R, 1992, The biology of breast tumor progression: acquistion of hormone independence and resistance to cytotoxic drugs. Acta Oncologica, 31, 115–23.Google Scholar
  6. 6.
    Thompson EW, Katz D, Shima TB, Wakeling AE, Lippman ME and Dickson RB, 1989, ICI-164,384, a pure antagonist of estrogen-stimulated MCF-7 cell proliferation and invasiveness. Cancer Res, 49, 6929–34.Google Scholar
  7. 7.
    Levi-Schaffer F and Kupietzky A, 1990, Mast cells enhance migration and proliferation of fibroblasts into an in vitrowound. Expt Cell Res, 188, 42–9.Google Scholar
  8. 8.
    Schleef RR and Birdwell CR, 1982, The effect on fibrin of endothelial cell migration in vitro. Tissue Cell, 14, 629–36.Google Scholar
  9. 9.
    Stewart RJ, Durley JA and Allardyce RA, 1979, The migration of fibroblasts into an in vitrowound. Br J Exptl Pathol, 60, 582–8.Google Scholar
  10. 10.
    Tchao R and Leighton J, 1979, The effect of vitamin A on the migration and DNA synthesis of rat bladder tumor cell line NBT II in culture. Invest Urol, 16, 478–82.Google Scholar
  11. 11.
    Jain PT, Pento JT, Magarian RA and Graves DC, 1991, Antiproliferative activity of a series of novel cyclopropyl antiestrogens on MCF-7 human breast cancer cells in culture. Anti-Cancer Drugs, 2, 487–93.Google Scholar
  12. 12.
    Jain PT, Pento JT and Magarian RA, 1994, A comparison of the antitumor activity of two triarylcyclopropyl antiestrogens (compounds 4d and 5c) on human breast cancer cells in culture. Anti-Cancer Drugs, 5, 429–36.Google Scholar
  13. 13.
    Burk RR, 1973, A factor from a transformed cell line that affects cell migration. Proc Natl Acad Sci USA, 70, 369–72.Google Scholar
  14. 14.
    Wakeling AE, 1993, The future of a new pure antiestrogen in clinical breast cancer. Breast Cancer Res Treat, 25, 1–9.Google Scholar
  15. 15.
    Pasqualini JR, Sumida C and Giambiagi N, 1988, Pharmacodynamics and biological effects of antiestrogens in different models. J Steroid Biochem, 31, 613–43.Google Scholar
  16. 16.
    Haar ET and Day BW, 1996, Cytostatic and cytotoxic action of Z-1,1-dichloro-2,3-diphenylcyclopropane in three human breast cancer cell lines. Anticancer Res, 16, 1107–16.Google Scholar
  17. 17.
    Coradini D, Biffi A, Cappelletti V and DiFronzo G, 1994, Activity of tamoxifen and new antiestrogens on estrogen receptor positive and negative breast cancer cells. Anticancer Res, 14, 1059–64.Google Scholar
  18. 18.
    Colletta AA, Benson JR and Baum M, 1994, Alternate mechanisms of action of anti-oestrogens. Breast Cancer Res Treat, 31, 5–9.Google Scholar
  19. 19.
    Manni A, Wright C and Buck H, 1991, Growth factor involvement in the multihormonal regulation of MCF-7 breast cancer cell growth in soft agar. Breast Cancer Res Treat, 20, 43–52.Google Scholar
  20. 20.
    Knabbe C, Lippman ME and Wakefield LM, 1987, Evidence that transforming growth factor is a hormonally regulated negative growth factor in human breast cancer cells. Cell, 48, 417–28.Google Scholar
  21. 21.
    Thompson EW, Reich R, Shima TB, et al. 1988, Differential regulation of growth and invasiveness of MCF-7 breast cancer cells by antiestrogens. Cancer Res, 48, 6764–8.Google Scholar
  22. 22.
    Knabe C, Zugmaier G, Schmahl M, Dietel M, Lippman ME and Dickson RB, 1991, Induction of TGF by antiestrogens droloxifene and toremifene in MCF-7 cells. Am J Clin Oncol, 14(suppl 2), s15-s20.Google Scholar
  23. 23.
    Pento JT, Magarian RA, Wright RJ, King MM and Benjamin EJ, 1981, Non-steroidal estrogens and antiestrogens: biological activity of cyclopropyl analogs of stilbene and stilbenediol. J Pharm Sci, 70, 399–403.Google Scholar
  24. 24.
    Jain PT, Pento JT, Magarian RA and Graves DC, 1991, Cyto-toxicity of Analog II in human breast cancer cells in culture. The Toxicologist, 11, 157.Google Scholar
  25. 25.
    Vasiliev JM, Gelfand IM, Dominina LV and Rappoport RI, 1969, Wound healing processes in cell cultures. Expt Cell Res, 54, 83–93.Google Scholar
  26. 26.
    Brunner N, Boysen B, Romer J and Spang-Thomsen M, 1993, The Nude mouse as an in vivomodel for breast cancer invasion and metastasis. Breast Cancer Res Treat, 24, 257–64.Google Scholar

Copyright information

© Chapman and Hall 1997

Authors and Affiliations

  • Annie C. Mathew
    • 1
  • Talitha T. Rajah
  • Gina M. Hurt
    • 1
  • S. M. Abbas Abidi
    • 1
  • John J. Dmytryk
    • 2
  • J. Thomas Pento
    • 1
  1. 1.Department of Pharmacology and Toxicology, College of PharmacyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  2. 2.Department of Periodontics, College of DentistryUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA

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