Clinical & Experimental Metastasis

, Volume 15, Issue 4, pp 432–439 | Cite as

Differential influence of antiestrogens on the in vitro release of gelatinases (type IV collagenases) by invasive and non-invasive breast cancer cells

  • S. M. Abbas Abidi
  • Eric W. Howard
  • John J. Dmytryk
  • J. Thomas Pento
Article

Abstract

Matrix metalloproteinases (MMPs) play an important role in tumor cell invasion and cancer metastasis. Accordingly, a higher level of these enzymes has been associated with the invasive phenotype. In the present study the effect of the antiestrogens, Analog II (AII), ICI-182,780 (ICI), and tamoxifen (TAM), on the in vitro release of MMPs, particularly gelatinases A and B by the MDA-MB-231 (MDA) and MCF-7 (MCF) human breast cancer cell lines was investigated using a solid-phase radioassay and substrate gel zymography. Quantitatively, the enzyme activity was found to be higher in the incubation medium from estrogen receptor (ER)-negative and more metastatic MDA cells compared to ER-positive and less metastatic MCF cells. Tissue inhibitor of metalloproteinases-1 (TIMP-1) reduced the enzyme activity in media from both MDA (56.36%) and MCF (71.03%) cells. Differential antiestrogen effects on the two cell lines were observed following 4 days of treatment of cells at a concentration of 10-6M. The enzyme activity from MDA cells was not influenced by treatment with any of the antiestrogens, whereas, in MCF cells, ICI produced the greatest enzyme inhibition (47.93%), followed by AII (36.51%) and TAM (24.05%). Concurrent treatment of MCF cells with 17-b-estradiol (10-9M) partially reversed the AII- and TAM-induced but did not alter ICI-induced inhibition of enzyme activity. Substrate gel zymography revealed that among the MMPs, the MDA cells released predominantly progelatinase A (72kDa) along with minor bands of activated forms, 62kDa and 59kDa, whereas progelatinase B (92kDa) was detected predominantly in the medium from MCF cells. Comparison of the overall antiestrogen effect indicates that ICI is the most potent inhibitor of enzyme activity in ER-positive MCF cells and that antiestrogen treatment may limit the metastatic potential of ER-positive breast cancer.

antiestrogens breast cancer gelatinases MCF-7 MDA-MB-231 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Liotta LA and Stetler-Stevenson WG, 1990, Metalloproteases and cancer invasion. Semin Cancer Biol, 99, 99–106.Google Scholar
  2. 2.
    Nakajima M, Welsch DR, Belloni PN and Nicolson GL, 1987, Degradation of basement membrane type IV collagen and lung subendothelial matrix by rat mammary adenocarcinoma cell clones of differing metastatic potentials. Cancer Res, 47, 4869–76.Google Scholar
  3. 3.
    Tryggvason K, Hoyhtya M and Salo T, 1987, Proteolytic degradation of extracellular matrix in tumor invasion. Biochem Biophys Acta, 907, 191–217.Google Scholar
  4. 4.
    Moll UM, Youngleib GL, Rosinski KB and Quigley JP, 1990, Tumor promoter stimulated Mr 92,000 gelatinase secreted by normal and malignant human cells: isolation and characterization of the enzyme from HT 1080 tumor cells. Cancer Res, 50, 6162–170.Google Scholar
  5. 5.
    Tryggvason K, Hoyhtya M and Pyke C, 1993, Type IV collagenases in invasive tumors. Breast Cancer Res Treat, 24, 209–18.Google Scholar
  6. 6.
    Nakajima M, Welsch DR, Wynn DM, Tsuruo T and Nicolson GL, 1993, Serum and plasma Mr 92,000 progelatinase levels correlate with spontaneous metastasis of rat 13762NF mammary adenocarcinoma. Cancer Res, 53, 5802–7.Google Scholar
  7. 7.
    Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM and Shafie S, 1980, Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature, 284, 67–8.Google Scholar
  8. 8.
    Angel P, Baumann I, Stein B, Delius H, Rahmsdorf HJ and Herrlich P, 1987, 12-O-Tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5′-flanking region. Mol Cell Biol, 7, 2256–66.Google Scholar
  9. 9.
    Webb P, Lopez GN, Uht RM and Kushner PJ, 1995, Tamoxifen activation of the estrogen receptor/AP-1 pathway: potential origin for the cell specific estrogenlike effects of antiestrogens. Mol Endocr, 9, 443–56.Google Scholar
  10. 10.
    Jordan VC, 1986, Estrogen/Antiestrogen Action and Breast Cancer Therapy. University of Wisconsin Press.Google Scholar
  11. 11.
    Fornander T, Cedermark B, Mattsson A, et al.1989, Adjuvant tamoxifen in early breast cancer: occupance of new primary cancers. Lancet, 1, 117–19.Google Scholar
  12. 12.
    Boccardo F, Bruzzi P, Rubagotti A, Nicolo G and Rosso R, 1989, Estrogen like action of tamoxifen on vaginal epithelium in breast cancer patients. Oncology, 38, 281–5.Google Scholar
  13. 13.
    Fentimen IS and Powles TJ, 1987, Tamoxifen and benign breast problems. Lancet, 2, 1070–1.Google Scholar
  14. 14.
    Killackey MA, Hakes TB and Pierce VK, 1985, Endometrial adenocarcinoma in breast cancer patients receiving antiestrogen. Cancer tiTreat Rep, 69, 237–8.Google Scholar
  15. 15.
    Black LJ, Jones CD and Falcone JF, 1983, Antagonism of estrogen action with new benzothiophene-derived antiestrogen. Life Sci, 32, 1031–6.Google Scholar
  16. 16.
    Day BW, Magarian RA, Jain PT, Pento JT, Mousissian GK and Meyer K, 1991, Synthesis and biological evaluation of a series of 1,1,-dichloro-2,2,3-triaryl cyclopropanes as pure antiestrogens. J Med Chem, 34, 842–51.Google Scholar
  17. 17.
    Stobaugh JF, Magarian RA and Pento JT, 1982, Synthesis and biological evaluation of gem-dichlorocyclopropyl analogs of stilbene congeners as potential antiestrogens. J Pharm Sci, 71, 1126–9.Google Scholar
  18. 18.
    Jain PT, Pento JT, Magarian RA and Graves DC, 1991, Cytotoxicity of AnalogII in human breast cancer cells in culture. The Toxicologist, 11, 157.Google Scholar
  19. 19.
    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
  20. 20.
    DeFriend DJ, Anderson E, Bell J, et al.1994, Effect of 4-hydroxytamoxifen and a novel pure antiestrogen (ICI-182,780) on the clonogenic growth of human breast cancer cells in vitro. Br J Cancer, 70, 204–11.Google Scholar
  21. 21.
    Hu FX, Veroni M, De Luise M, et al.1993, Circumvention of tamoxifen resistance by the pure antiestrogen ICI-182,780. Int J Cancer, 55, 873–6.Google Scholar
  22. 22.
    Jain PT and Pento JT, 1991, A vehicle for the evaluation of hydrophobic compounds in cell culture. Res Comm Chem Path Pharm, 74, 105–16.Google Scholar
  23. 23.
    Howard EW, Bullen EC and Banda MJ, 1991, Regulation of the autoactivation of human 72 kDa progelatinase by tissue inhibitor of metalloproteinase-2. J Biol Chem, 226, 13064–9.Google Scholar
  24. 24.
    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
  25. 25.
    Heussen C and Dowdle EB, 1980, Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates. Analyt Biochem, 102, 196–202.Google Scholar
  26. 26.
    Kao RT and Stern R, 1986, Collagenases in human breast carcinoma cell lines. Cancer Res, 46, 1349–54.Google Scholar
  27. 27.
    Brown PD, Levy AT, Margulies IMK, Liotta LA and Stetler-Stevenson WG, 1990, Independent expression and cellular processing of Mr 72 kDa type IV collagenase and interstitial collagenase in human tumorigenic cell lines. Cancer Res, 50, 6184–91.Google Scholar
  28. 28.
    Overall CM, Wrana JL and Sodek J, 1989, Independent regulation of collagenase, 72 kDa progelatinase and metalloendoproteinase inhibitor expression in human fibroblasts by transforming growth factor-β. J Biol Chem, 264, 1860–9.Google Scholar
  29. 29.
    Duffy MJ, 1992, The role of proteolytic enzymes in cancer invasion and metastasis. Clin Exp Metastasis, 10, 145–55.Google Scholar
  30. 30.
    Mueller SC, Yeh Y and Chen WT, 1992, Tyrosine phosphate regulation of membrane proteins mediates cellular invasion by transformed cells. J Cell Biol, 119, 1319–25.Google Scholar
  31. 31.
    Monsky WL, Kelly T, Lin CY, et al.1993, Binding and localization of Mr 72,000 matrix metalloproteinase at cell surface invadopodia. Cancer Res, 53, 3159–64.Google Scholar
  32. 32.
    Emonard HP, Remacle AG, Noel AC, Grimand JA, Stetler-Stevenson WG and Foidart JM, 1992, Tumor cell surface associated receptor for the Mr 72,000 type IV collagenase. Cancer Res, 52, 5845–8.Google Scholar
  33. 33.
    Abidi SMA, Howard EW and Pento JT, 1996, Influence of antiestrogens on the release of plasminogen activator by human breast cancer cells. AACR Special Conference: Proteases and Protease Inhibitors, A–45.Google Scholar
  34. 34.
    Paranjpe M, Engel L, Young N and Liotta LA, 1980, Activation of human breast carcinoma collagenase through plasminogen activator. Life Sci, 26, 1223–31.Google Scholar
  35. 35.
    Katzenellenbogen BS, Norman JM, Eckert RL, Peltz SW and Mangel WF, 1984, Bioactivities, estrogen receptor interaction and plaminogen activatorinducing activities of tamoxifen and hydroxytamoxifen isomers in MCF-7 human breast cancer cells. Cancer Res, 44, 112–19.Google Scholar
  36. 36.
    Black LJ and Goode RL, 1981, Evidence for biological action of the antiestrogens LY117018 and tamoxifen by different mechanisms. Endocrinology, 109, 987–9.Google Scholar
  37. 37.
    Turner R and Tjian R, 1989, Leucine repeats and an adjacent DNA binding domain mediate the formation of functional cfos-cjun heterodimers. Science, 243, 1689–94.Google Scholar
  38. 38.
    Sassone-Corsi P, Lamph WW, Kamps M and Verma IM, 1988, Fos-associated cellular p35 is related to nuclear transcription factor AP-1. Cell, 54, 553–60.Google Scholar
  39. 39.
    Huhtala P, Chow LT and Tryggvason K, 1990, Structure of the human type IV collagenase gene. J Biol Chem, 265, 11077–82.Google Scholar
  40. 40.
    Huhtala P, Tuuttila A, Chow LT, Lohi J, Keski-Oja J and Tryggvason K, 1991, Complete structure of the human gene for 92kDa type IV collagenase. Divergent regulation of expression for the 92-and 72-kilodalton enzyme genes in HT-1080 cells. J Biol Chem, 266, 16485–90. 1 1 1 1Google Scholar

Copyright information

© Chapman and Hall 1997

Authors and Affiliations

  • S. M. Abbas Abidi
    • 1
  • Eric W. Howard
    • 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 Pathology, College of MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA

Personalised recommendations