Chemically modified tetracyclines inhibit human melanoma cell invasion and metastasis

Springer Science and Business Media LLC - 1998
Richard E. B. Seftor1, Elisabeth A. Seftor1, Joseph E. De Larco2, David E. Kleiner3, Jill Leferson3, William G. Stetler-Stevenson3, Thomas F. McNamara4, Lorne M. Golub4, Mary J. C. Hendrix1
1Department of Anatomy and Cell Biology, College of Medicine Iowa Cancer Center, Iowa City, USA
2Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, USA
3Extracellular Matrix Pathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, USA
4Department of Oral Biology and Pathology, Stony Brook School of Dental Medicine, State University of New York, Stony Brook, USA

Tóm tắt

Recent work has shown that chemically modified tetracyclines (CMTs) are potent inhibitors of matrix metal-loproteinase (MMP) activity, both in vitro and in vivo, which is distinct from their antimicrobial activities (Golub et al. Crit Rev Oral Biol Med, 2, 297-321, 1991; Ryan et al. Curr Opin Rheumatol, 8, 238-47, 1996). The process of tumor cell invasion requires MMP-mediated degradation of extracellular matrix barriers as a key step in the metastasic cascade. In this study, we examined the effect(s) of doxycycline and CMTs on extracellular levels of gelatinase A and B activity from a highly invasive and metastatic human melanoma cell line C8161, and correlated these observations with changes in the cells' biological behavior in an in vitro invasion assay and in an in vivo SCID mouse model. The results indicate that coincident with the ability of these compounds to differentially suppress extracellular levels of gelatinase activity, C8161 cells treated with doxycycline, CMT-1, CMT-3, or CMT-6 were less invasive in vitro in a dose-dependent manner (3-50 mg/ml). Furthermore, data derived from the in vivo model indicate that SCID mice dosed orally with CMT-1 or CMT-3 contained a reduced number of lung metastases following i.v. injection of C8161 cells via tail vein inoculation. These observations suggest that careful screening of different CMTs could lead to the identification of compounds which suppress the formation and magnitude of metastases associated with certain cancers, and if used as an adjunct to other treatment regimes, lead to greater efficacy in the treatment of metastatic cancers. © Rapid Science 1998

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Tài liệu tham khảo

Liotta LA, Rao CN and Wewer UM, 1986, Biochemical interactions of tumor cells with the basement membrane. Ann Rev Biochem, 55, 1037-57.

Stetler-Stevenson WG, Liotta LA and Kleiner DE Jr, 1993, Extracelluar matrix 6: role of matrix metalloproteinases in tumor invasion and metastasis. FASEB J, 7, 1434-41.

Cockett MI, Birch ML, Murphy G, Hart IR and Docherty AJ, 1994, Metalloproteinase domain structure, cellular invasion and metastasis. Biochem Soc Trans, 22, 55-7.

Noel A, Emonard H, Pollette M, Birembaut P and Foidart JM, 1994, Role of matrix, fibroblasts and type IV collagenases in tumor progression and invasion. Path Res Pract, 190, 934-41.

Himelstein BP, Canete-Solar R, Bernhard EJ, Dilks DW and Muschel RJ, 1994-95, Metalloproteinases in tumor progression: the contribution of MMP-9. Inv Metast, 14, 246-58.

Kohn EC and Liotta, 1995, Molecular insights into cancer invasion: strategies for prevention and intervention. Cancer Res, 55, 1856-62.

Stetler-Stevenson WG, Hewitt R and Corcoran M, 1996, Matrix metalloproteinases and tumor invasion: from correlation and causality to the clinic. Sem Cancer Biol, 7, 147-54.

Golub LM, Ramamurthy NS, McNamara TF, Greenwald RA and Rifkin BR, 1991, Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs. Crit Rev Oral Biol Med, 2, 297-321.

Ryan ME, Greenwald RA and Golub LM, 1996, Potential of tetracyclines to modify cartilage breakdown in osteoarthritis. Curr Opin Rheumatol, 8, 238-47.

Yu Z, Leung MK, Ramamurthy NS, McNamara TF and Golub LM, 1992, HPLC determination of a chemically modified nonantimicrobial tetracycline: biological implications. Biochem Med Metab Biol, 47, 10-20.

Golub LM, Evans RT, McNamara TF, Lee HM and Ramamurthy NS, 1994, A non-antimicrobial tetracycline inhibits gingival matrix metalloproteinases and bone loss in Porphyromonas gingivalis-induced periodontitis in rats. Ann NY Acad Sci, 732, 96-111.

Rifkin BR, Vernillo AT and Golub LM, 1993, Blocking periodontal disease progression by inhibiting tissue-destructive enzymes: a potential therapeutic role for tetracyclines and their chemically-modified analogs. Am Acad Period, 64, 819-27.

Zucker S, Lysik RM, Ramamurthy NS, Golub LM, Wieman JM and Wilkie DP, 1985, Diversity of melanoma plasma membrane proteinases: inhibition of collagenolytic and cytolytic activities by minocycline. J Natl Cancer Inst, 75, 517-25.

Zucker S, Wieman J, Lysik RM, et al. 1989, Gelatin-degrading type IV collagenase isolated from human small cell lung cancer. Inv Metast, 9, 167-81.

Rifkin BR, Vernillo AT, Golub LM and Ramamurthy NS, 1994, Modulation of bone resorption by tetracyclines. Ann NY Acad Sci, 732, 165-80.

Nip LH, Uitto V-J and Golub LM, 1993, Inhibition of epithelial cell matrix metalloproteinases by tetracyclines. J Periodont Res, 28, 379-85.

Fridman R, Fuerst TR, Bird RE, et al. 1992, Domain structure of human 72-kDa gelatinase/type IV collagenase. Characterization of proteolytic activity and identification of the tissue inhibitor of metalloproteinase-2 (TIMP-2) binding regions. J Biol Chem, 267, 15398-405.

Seftor REB, Seftor EA, Gehlsen KR, et al. 1992, Role of the avb3 integrin in human melanoma cell invasion. Proc Natl Acad Sci USA, 89, 1557-61.

Seftor REB, Seftor EA, Stetler-Stevenson WG and Hendrix MJC, 1993, The 72 kDa type IV collagenase is modulated via differential expression of ?v?3 and a5b1 integrins during human melanoma cell invasion. Cancer Res, 53, 3411-15.

Hendrix MJC, Seftor EA, Seftor REB and Fidler IJ, 1987, A simple quantitative assay for studying the invasive potential of high and low human metastatic variants. Cancer Lett, 38,137-47.

Thorgeirsson UP, Lindsay CK, Cottam DW and Gomez DE, 1993, Tumor invasion, proteolysis, and angiogenesis. J Neuro-Oncol, 18, 89-103.

Yu M, Sato H and Thompson EW, 1995, Complex regulation of membrane-type matrix metalloproteinase expression and matrix metalloproteinase-2 activation by concanavalin A in MDA-MB-321 human breast cancer cells. Cancer Res, 55(15), 3272-7.

Lim YT, Sugiura Y, Laug WE, Sun B, Garcia A and DeClerck YA, 1996, Independent regulation of matrix metalloproteinases and plasminogen activators in human fibrosarcoma cells. J Cell Physiol, 167, 333-40.

Smith GN Jr, Brandt KD and Hasty KA, 1994, Procollagenase is reduced to inactive fragments upon activation in the presence of doxycycline. Ann NY Acad Sci, 732, 436-8.

Smith GN Jr, Brandt KD and Hasty KA, 1996, Activation of recombinant human neutrophil procollagenase in the presence of doxycycline results in fragmentation of the enzyme and loss of enzyme activity. Arthrit Rheumat, 39, 235-44.

Sorsa T, Konttinen YT, Lindy O, et al. 1993, Doxycycline protects serum alpha-1-antitrypsin from human neutrophil collagenase. Agents Actions Suppl, 39, 225-9.

Welch DR, Bisi JE, Miller BE, et al. 1991, Characterization of a highly invasive and spontaneously metastatic human malignant melanoma cell line. Int J Cancer, 47, 227-37.

Yeatman TJ and Nicolson GL, 1993, Molecular basis of tumor progression: mechanisms of organ-specific tumor metastasis. Sem Surg Oncol, 9, 256-63.

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