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Cancer metastasis: Biological and clinical aspects

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Abstract

The main cause of morbidity and mortality in cancer is the formation of distant metastases. While alterations in c-oncogenes, tumour suppressor genes and DNA repair enzymes are the key molecules involved in carcinogenesis, increased expression of proteases, motility factors and altered expression of adhesion molecules are causally involved in metastasis. The proteases mediating metastasis include urokinase plasminogen activator, cathepsin B, D and L and various matrix metalloproteinases. Certain proteases involved in metastasis (e.g., urokinase plasminogen activator) have been shown to be strong and independent prognostic markers for a variety of cancers. Finally, molecules involved in cancer spread are potential targets for new forms of antimetastatic therapies.

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References

  1. Fidler, I. J. Critical factors in the biology of human cancer metastasis. Twenty-eighth G. H. A. Clowes memorial Lecture. Cancer Res. 1990; 50: 6130–6138.

    PubMed  CAS  Google Scholar 

  2. Fidler, I. J. Metastasis: Quantitative analysis of distribution and fate of tumor cell emboli labelled with125I-5-iododeoxyuridine. J. Natl. Cancer Inst. (U.S.). 1970; 45: 773–782.

    CAS  Google Scholar 

  3. Folkman, J., Shing, Y. Angiogenesis. J. Biol. Chem. 1992; 267: 10931–10934.

    PubMed  CAS  Google Scholar 

  4. Fett, J. W., Strydom, D. L., Lob., R. R., Alderman, E. M., Bethune, J. L., Riordan, J. F., Valee, B. L. Isolation and characterisation of angiogenin, an angiogenic protein from human carcinoma cells. Biochemistry 1985; 24: 5480–5486.

    Article  PubMed  CAS  Google Scholar 

  5. O’Reilly, M. S., Holmgren, L., Shing, Y., Chen, C., Rosenthal, R. A., Moses, M. et al. Angiostastin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994; 79: 315–328.

    Article  PubMed  CAS  Google Scholar 

  6. O’Reilly, M. S., Holmgren, L., Chen, C., Folkman, J. Angiostatin induces and sustains dormancy of human pituitary tumors in mice. Nature Med. 1996; 2: 689–692.

    Article  PubMed  CAS  Google Scholar 

  7. O’Reilly, M. S., Boehm, T., Shing, Y., Fukai, N., Vasios, G. et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997; 88: 277–285.

    Article  PubMed  CAS  Google Scholar 

  8. Duffy, M. J. Role of proteolytic enzymes in cancer invasion and metastasis. Clin. Exp. Metastasis 1992; 10: 145–155.

    Article  PubMed  CAS  Google Scholar 

  9. Duffy, M. J. The biochemistry of metastasis. Adv. Clin. Chem. 1996; 32: 135–166.

    Article  PubMed  CAS  Google Scholar 

  10. Duffy, M. J. Urokinase plasminogen activator and malignancy. Fibrinolysis 1993; 7: 295–302.

    Article  CAS  Google Scholar 

  11. Andreason, P. A., Kjoller, L., Christiansen, L., Duffy, M. J. The urokinase-type plasminogen activator system in cancer metastasis: a review. Int. J. Cancer 1997; 72: 1–22.

    Article  Google Scholar 

  12. Sloane, B. F., Moin, K., Krepela, E., Rozhin, J. Cathepsin B and its endogenous inhibitors: The role in tumor malignancy, Cancer Metastasis Rev. 1990; 9: 333–352.

    Article  PubMed  CAS  Google Scholar 

  13. Garcia, M., Platet, N., Liaudet, E., Laurent, V., Derocq, D., Brouillet, J-P., Rochefort, H. Biological and clinical significance of Cathepsin D in breast cancer metastasis. Stem Cells 1996; 14:642–650.

    Article  PubMed  CAS  Google Scholar 

  14. MacDougall, J. R., Matrisian, L. M. Contribution of tumor and stromal matrix metalloproteinases to tumor progression invasion and metastasis. Cancer Met. Rev. 1995; 14: 351–362.

    Article  CAS  Google Scholar 

  15. Menger, M. D., Vollmar, B. Adhesion molecules as determinants of disease from molecular biology to surgical research. Br. J. Surg. 1996; 83: 588–601.

    Article  PubMed  CAS  Google Scholar 

  16. Frenette, P. S., Wagner, D. D. Adhesion moleucles. N. Engl. J. Med. 1996; 334: 1526–1529.

    Article  PubMed  CAS  Google Scholar 

  17. Berg, E. L., McEvoy, L., Berlin, C., Bargatze, R., Butcher, E. C. L-selectin-mediated lymphocyte rolling on MadCAM-1. Nature (London) 1993; 366: 695–698.

    Article  CAS  Google Scholar 

  18. Duffy, M. J., O’Grady, P., Devaney, D., O’Siorain, L., Fennelly, J. J., Lijnen, H. R. Urokinase-plasminogen activator, a marker for aggressive breast cancers, preliminary report. Cancer (Philadelphia) 1988; 62: 531–533.

    Article  CAS  Google Scholar 

  19. Duffy, M. J., Reilly, D., O’Sullivan, C., O’Higgins, N., Fennelly, J. J., Andreasen, P. Urokinase plasminogen activator, a new and independent prognostic marker in breast cancer. Cancer Res. 1990; 50: 6827–6829.

    PubMed  CAS  Google Scholar 

  20. Duffy, M. J. Proteases as prognostic markers in cancer. Clin. Cancer Res. 1996; 2: 613–618.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Nuclear Medicine, St. Vincent’s Hospital, Dublin 4

    M. J. Duffy

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  1. M. J. Duffy
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Conway Review Lecture, 1997

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Duffy, M.J. Cancer metastasis: Biological and clinical aspects. I.J.M.S. 167, 4–8 (1998). https://doi.org/10.1007/BF02937542

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