Skip to main content
Log in

The role of proteolytic enzymes in cancer invasion and metastasis

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

The production of metastasis appears to involve a number of different proteases including the urokinase form of plasminogen activator, cathepsin B, cathepsin D and various metalloproteases. Early data implicating these proteases in metastasis were mostly indirect and based on correlation studies in animal models. More recent work, using specific protease inhibitors and antibodies against proteases to block experimental metastasis, have provided more direct evidence that proteases play a role in cancer spread. In addition, transfection of genes encoding certain proteases increases the metastatic phenotype of the recipient cells. In human tumours, a number of different proteases also correlate with metastatic potential. It is concluded that certain proteases may be new prognostic markers in cancer as well as new targets for anti-metastatic therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Tarin D, 1985, Clinical and experimental studies on the biology of metastasis.Biochimica et Biophysica Acta,780, 227–235.

    Google Scholar 

  2. Fidler IJ, 1990, Critical factors in the biology of human cancer metastasis: twenty-eight GHA Clowes memorial award lecture.Cancer Research,50, 6130–6138.

    Google Scholar 

  3. Tryggvason K, Hoyhtya M and Salo T, 1987, Proteolytic degradation of extracellular matrix in tumor invasion.Biochimica et Biophysica Acta,907, 191–207.

    Google Scholar 

  4. Timpl R, 1989, Structure and biological activity of basement membrane proteins.European Journal of Biochemistry,180, 487–502.

    Google Scholar 

  5. Duffy MJ, 1990, Plasminogen activators and cancer.Blood Coagulation and Fibrinolysis, 1, 681–687.

    Google Scholar 

  6. Testa JE and Quigley JP, 1990, The role of urokinase-type plasminogen activator in aggressive tumor cell behavior.Cancer Metastasis Reviews,9, 353–367.

    Google Scholar 

  7. Stoppelli MP, Corti A, Soffientini A, Cassani G, Blasi F and Assoian RK, 1985, Differentiation enhanced binding of the amino terminal fragment of human urokinase plasminogen activator to a specific receptor on 11937 monocytes.Proceedings of the National Academy of Sciences, USA,82, 4939–4943.

    Google Scholar 

  8. Vassali J-D, Baccino D and Belin D, 1985, A cellular binding site for the Mr 55,000 form of the human plasminogen activator.Journal of Cell Biology,100, 86–92.

    Google Scholar 

  9. Ossowski L, 1988,In vivo invasion of modified chorioallantoic membrane by tumor cells: the role of cell surface-bound urokinase.Journal of Cell Biology,107, 2437–2445.

    Google Scholar 

  10. Sloane BF, Moin K, Krepela E and Rozhin J, 1990, Cathepsin B and its endogenous inhibitors: the role in tumor malignancy.Cancer Metastasis Reviews,9, 333–352.

    Google Scholar 

  11. Nishimura Y, Kawabata T and Kato K, 1988, Identification of latent procathepsin B and L in microsomal lumen.Archives of Biochemistry and Biophysics,261, 64–71.

    Google Scholar 

  12. Hara K, Kominami E and Katunuma N, 1988, Effect of proteinase inhibitors on intracellular processing of cathepsin B, H and L in rat macrophages.FEBS Letters,231, 229–231.

    Google Scholar 

  13. Eeckhout Y and Vaes G, 1977, Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Effects of lysosomal cathepsin B, plasmin and kallikrein and spontaneous activation.Biochemical Journal,36, 1555–1563.

    Google Scholar 

  14. Kobayashi H, Schmitt M, Goretzki L, Chuchowolski N, Calvete J, Kramer M, Gunzler WA, Janicke F and Graeff H, 1991, Cathepsin B efficiently activates the soluble and the tumor cell receptor-bound form of the proenzyme urokinase-type plasminogen activator (pro-uPA).Journal of Biological Chemistry, 266, 5147–5152.

    Google Scholar 

  15. Sloane BF, Rozhin J, Johnson K, Taylor H, Crissman J and Honn KV, 1986, Cathepsin B: association with plasma membrane in metastatic tumors.Proceedings of the National Academy of Sciences, USA,83, 2483–2487.

    Google Scholar 

  16. Keren Z and LeGrue SJ, 1988, Identification of cell surface cathepsin B-like activity on murine melanomas and fibrosarcomas: modulation by butanol extraction.Cancer Research,48, 1416–1421.

    Google Scholar 

  17. Pagano M, Dalet-Fumeron V and Engler R, 1989, The glycosylation state of the precursors of the cathepsin-like proteinase from human malignant as citic fluid: possible implication in the secretory pathways of these proenzymes. Cancer Letters, 45, 13–19.

    Google Scholar 

  18. Westley B and Rochefort H, 1980, A secreted glycoprotein induced by estrogen in human breast cancer cell lines.Cell,20, 52–362.

    Google Scholar 

  19. Vignon F, Capony F, Chambon M, Freiss G, Garcia M, and Rochefort H, 1986, Autocrine growth stimulation on the MCF7 breast cancer cells by the estrogen-regulated 52K protein.Endocrinology,118, 1517–1545.

    Google Scholar 

  20. Briozzo P, Morisset M, Capony F, Rougeot C and Rochefort H, 1988,In vitro degradation of extracellular matrix with Mr 52,000 cathepsin D secreted by breast cancer cells.Cancer Research,48, 3688–3692.

    Google Scholar 

  21. Rochefort H, Capony F and Garcia M, 1990, Cathepsin D: a protease involved in breast cancer metastasis.Cancer Metastasis Reviews,9, 321–331.

    Google Scholar 

  22. Capony F, Rougeot P, Montcourrier P, Cavailles V, Salazar G and Rochefort H, 1989, Increased secretion, altered processing, and glycosylation of proca thepsin D in human mammary cancer cells.Cancer Research,49, 3904–3909.

    Google Scholar 

  23. Murphy G, Reynolds JJ and Hembry RM, 1989, Metalloproteases and cancer invasion and metastasis.International Journal of Cancer,44, 757–760.

    Google Scholar 

  24. Liotta L, Tryggvason K, Garbisa S, Gehron-Ribey P and Abe S, 1981, Partial purification and characterization of a neutral protease which cleaves type IV collagen.Biochemistry,20, 100–104.

    Google Scholar 

  25. Wilhelm SM, Collier IE, Marmer BL, Eisen AZ, Grant GA and Goldberg GI, 1989, SV40 transformed human lung fibroblasts secrete a 92 kDa type IV collagenase which is identical to that secreted by normal human macrophages.Journal of Biological Chemistry,264, 17213–17221.

    Google Scholar 

  26. Kato Y, Ogawa K, Yamomoto S, Abe S, Kishi J and Hayakawa T, 1990, A novel TIMP-insensitive type IV collagen-degrading metalloprotease from murine metastatic sarcoma cells.FEBS Letters,268, 39–42.

    Google Scholar 

  27. McDonnell S and Matrisian LM, 1990, Stromelysin in tumor progression and metastasis.Cancer Metastasis Reviews,9, 305–319.

    Google Scholar 

  28. Basset P, Bellocq JP, Wolf C, Stoll I, Hutin P, Limacher J, Podhajeer O, Chenard M, Rio M and Chambon P, 1990, A novel metalloprotease gene specifically expressed in stromal cells of breast carcinomas.Nature,348, 699–704.

    Google Scholar 

  29. Saksela O, 1985, Plasminogen activation and regulation of pericellular proteolysis.Biochimica et Biophysica Acta,823, 35–65.

    Google Scholar 

  30. Duffy MJ, 1987, Do proteases play a role in cancer invasion and metastasis?European Journal of Cancer and Clinical Oncology,23, 583–589.

    Google Scholar 

  31. Wang BS, McLoughlin GA, Richie JP and Mannick JA, 1980, Correlation of the production of plasminogen activator with tumor metastasis in B16 mouse melanoma cell lines.Cancer Research,40, 288–292.

    Google Scholar 

  32. Sloane BF, Dunn JR and Horn KV, 1981, Lysosomal cathepsin B: correlation with metastatic potential.Science,212, 1151–1153.

    Google Scholar 

  33. Liotta L, Tryggvason K, Garbisa S, Hart I, Foltz C and Shafie S, 1980, Metastatic potential correlates with enzymatic degradation of basement membrane collagen.Nature,284, 67–68.

    Google Scholar 

  34. Qian F, Bajkowski As, Steiner DF, Chan SJ and Frankfater A, 1989, Expression of 5 cathepsins in murine melanomas of varying metastatic potential and normal tissue.Cancer Research,49, 4870–4875.

    Google Scholar 

  35. Carlsen SA, Ramshaw IA and Warrington RC, 1984, Involvement of plasminogen activator production with tumor metastasis in a rat model.Cancer Research,44, 3012–3016.

    Google Scholar 

  36. Eisenbach L, Segal S and Feldman M, 1985, Proteolytic enzymes in tumor metastasis. 1. Plasminogen activator in clones of Lewis lung carcinoma and T10 sarcoma.Journal of the National Cancer Institute,74, 77–85.

    Google Scholar 

  37. Tarin D, Hoyt BJ and Evan DJ, 1982, Correlation of collagenase secretion with metastatic colonization in naturally-occurring murine mammary tumours.British Journal of Cancer,46, 266–278.

    Google Scholar 

  38. Sekiya S, Oosaki T and Suzuki N, 1985, Invasion potential of human choriocarcinoma cell lines and the role of lytic enzymes.Gynecology and Oncology,22, 324–333.

    Google Scholar 

  39. Koppel P, Baici A, Keist R, Matzku S and Keller R, 1984, Cathepsin B-like proteinase as a marker for metastatic tumor cell variants.Experimental Cell Biology,52, 293–299.

    Google Scholar 

  40. Zucker S, Beck G, Distefano JF and Lysik RM, 1985, Role of different cell proteinases in cancer invasion and cytolysis.British Journal of Cancer,52, 223–232.

    Google Scholar 

  41. Lowe FC and Issacs JT, 1984, Biochemical methods for predicting metastatic ability of prostatic cancer utilizing the Dunning R-3327 rat prostatic adenocar cinoma system as a model.Cancer Research,44, 744–752.

    Google Scholar 

  42. Bernhard EJ, Muschel RJ and Hughes EN, 1990, Mr 92,000 gelatinase release correlates with the metastatic phenotype in transformed rat embryo cells.Cancer Research,50, 3872–3877.

    Google Scholar 

  43. Nakajima M, Irimura T and Nicolson GL, 1988, Heparanases and tumor metastasis.Journal of Cell Biochemistry,36, 157–167.

    Google Scholar 

  44. Garbisa S, Pozzatti R, Muschel R, Saffiotti U, Ballin M and Goldfarb R, 1987, Secretion of type IV collagenolytic protease and metastatic phenotype: induction by transfection with c-Ha-ras but not c-Ha-ras plus Ad2-Ela.Cancer Research,47, 1523–1528.

    Google Scholar 

  45. Halaka A, Bunning R, Bird CC, Gibson M and Reynolds JJ, 1983, Production of collagenase and inhibitor TIMP by intracranial tumors and durain vitro.Journal of Neurosurgery,59, 461–466.

    Google Scholar 

  46. Hicks NJ, Ward RV and Reynolds JJ, 1984, A fibrosarcoma model derived from mouse embryo cells: growth properties and secretion of collagenase and metalloproteinase inhibitor (TIMP) by tumour cell lines.International Journal of Cancer,33, 835–844.

    Google Scholar 

  47. Khokha R, Waterhouse P, Yagel S, Lala PK, Overall CM, Norton G and Denhardt DT, 1989, Antisense RNA-induced reduction in murine TIMP level confers oncogenicity on Swiss 3T3 cells.Science,243, 947–950

    Google Scholar 

  48. Khokha R and Denhardt DT, 1989, Matrix metalloproteinases and tissue inhibitors of metalloproteinases: a review of their role in tumorigenesis and tissue invasion.Invasion and Metastasis,9, 391–405.

    Google Scholar 

  49. Rozhin J, Gomez AP, Ziegler GH, Nelson KK, Chang YS, Fong D, Onoda J, Honn KV and Sloane BF, 1990, Cathepsin B to cysteine proteinase inhibitor balance in metastatic cell subpopulations isolated from murine tumors.Cancer Research,50, 6278–6284.

    Google Scholar 

  50. Neri A, Bohoslawec O, Anderson TD and Tokes ZA, 1991, Differential release of active proteinase inhibitors by two rat mammary adenocarcinoma variants possessing different metastatic potential.Cancer Research,51, 1318–1325.

    Google Scholar 

  51. Lah TT, Clifford JL, Helmer KM, Day NA, Moin K, Honn KV, Crissman JD and Sloane BF, 1989, Inhibitory properties of low molecular mass cysteine proteinase inhibitors from human sarcoma.Biochimica et Biophysica Acta,993, 63–73.

    Google Scholar 

  52. Janicke F, Schmitt M and Graeff H, 1991, Clinical relevance of the urokinase-type and tissue-type plasminogen activators and their type 1 inhibition in breast cancer.Seminars in Thrombosis and Hemostasis,17, 302–312.

    Google Scholar 

  53. Reilly D, Andreasen P and Duffy MJ, 1989, Studies on plasminogen activator inhibitor PAI-1 in human breast cancer.Biochemical Society Transactions,17, 609.

    Google Scholar 

  54. Mignatti P, Robbins E and Rifkin DB, 1986, Tumor invasion through the human amniotic membrane: requirement for a proteinase cascade.Cell,47, 487–498.

    Google Scholar 

  55. Cajot JF, Bamat J, Bergonzelli GE, Kruithof E, Medcalf RI, Tetuz J and Sordat B, 1990, Plasminogen activator inhibitor type 1 is a potent natural inhibitor of extracellular matrix degradation by fibrosarcoma and colon carcinoma cells.Proceedings of the National Academy of Sciences, USA,87, 6939–6943.

    Google Scholar 

  56. Baker MS, Bleakley P, Woodrow GC and Doe WF, 1990, Inhibition of cancer cell urokinase by its specific inhibitor PAI-2 and subsequent effects on extracellular matrix degradation.Cancer Research,50, 4676–4684.

    Google Scholar 

  57. DeClerck YA, Yean T-D, Chan D, Shimada H and Langley KE, 1991, Inhibition of tumor invasion of smooth muscle cell layers by recombinant human metalloproteinase inhibitor.Cancer Research,51, 2151–2157.

    Google Scholar 

  58. Schultz RM, Silberman S, Persky B, Bajowski A and Carmichael D, 1988, Inhibition by human recombinant tissue inhibitor of metalloproteinases of human amnion invasion and lung colonization by murine B16-F1O melanoma cells.Cancer Research,48, 5539–5545.

    Google Scholar 

  59. Alvarez OA, Carmichael DF and DeClerck YA, 1990, Inhibition of collagenolytic ;activity and metastasis of tumor cells by a recombinant human tissue inhibitor of metalloproteinases.Journal of the National Cancer Institute,82, 589–595.

    Google Scholar 

  60. Ossowski L and Reich E, 1983, Antibodies to plasminogen activator inhibit human tumor metastasis.Cell,35, 611–619.

    Google Scholar 

  61. Ossowski L, Russo-Payne H and Wilson EL, 1991, Inhibition of urokinase-type plasminogen activator by antibodies: the effect on dissemination of a human tumor in the nude mouse model.Cancer Research,51, 274–281.

    Google Scholar 

  62. Hearing VJ, Law L, Corti A, Appella E and Blasi F, 1988, Modulation of metastatic potential by cell surface urokinase of murine melanoma cells.Cancer Research,48, 1270–1278.

    Google Scholar 

  63. Hoyhtya M, Hujanen E and Turpeenniemi-Hujanen T, 1990, Modulation of type IV collagenase and invasive behaviour of metastatic melanoma (A2058) cells in vitro by monoclonal antibodies to type IV collagenase.International Journal of Cancer,46, 282–286.

    Google Scholar 

  64. Kodama Y and Tanaka T, 1978, Effect of urokinase on growth and metastasis of rabbit V2 carcinoma.Gann,69, 9–15.

    Google Scholar 

  65. Tanaka N, Ogawa H, Tanaka K, Kinjo M and Kohga S, 1981, Effects of tranexamic acid and urokinase on hematogenous metastases of Lewis lung carcinoma in mice.Invasion and Metastasis,1, 149–157.

    Google Scholar 

  66. Nierodzik ML, Plotkin A, Kajumo F and Karpatkin S, 1991, Thrombin stimulates tumor-platelet adhesionin vitro and metastasisin vitro.Journal of Clinical Investigations,87, 229–236.

    Google Scholar 

  67. Axelrod JH, Reich R and Miskin R, 1989, Expression of human recombinant plasminogen activator enhances invasion and experimental metastasis of H-ras-transformed NIH 3T3 cells.Molecular Cell Biology,9, 2133–2141.

    Google Scholar 

  68. Cajot J-F, Schleuning W-D, Medcalf RL, Bamat J, Tetuz J, Libermann L and Sordat B, 1989, Mouse L-cells expressing human prourokinase-type plasminogen activator: effects on extracellular matrix degradation and invasion.Journal of Cell Biology,109, 915–925.

    Google Scholar 

  69. Yu H and Schultz RM, 1990, Relationship between secreted urokinase plasminogen activator activity and metastatic potential in murine B16 cells transfected with human urokinase sense and antisense genes.Cancer Research,50, 7623–7633.

    Google Scholar 

  70. Garcia M, Derocq D, Pujol P and Rochefort H, 1990, Overexpression of transfected cathepsin D in transformed cells increases their malignant phenotype and metastatic potency.Oncogene,5, 1809–1814.

    Google Scholar 

  71. Skriver L, Larsson L, Kielberg V, Nielsen LS, Andresen PB, Kristensen P and Dano K, 1984, Immunocytochemical localisation of urokinase type plasminogen activator in Lewis lung carcinoma.Journal of Cell Biology,99, 753–758.

    Google Scholar 

  72. Kristensen P, Pyke C, Lund LR, Andreasen PA and Dano K, 1990, Plasminogen activator inhibitor type 1 in Lewis lung carcinoma.Histochemistry,93, 559–566.

    Google Scholar 

  73. Baici A, Gyger-Marazzi M and Strauli P, 1984, Extracellular cysteine proteinase and collagenases activities as a consequence of tumor-host interaction in the rabbit V2 carcinoma.Invasion and Metastasis,4, 13–27.

    Google Scholar 

  74. Koivunen E, Huhtala M-L and Stenman U-H, 1989, Human ovarian tumor-associated trypsin.Journal of Biological Chemistry,264, 14095–14099.

    Google Scholar 

  75. Kirchheimer JC, Wojta J, Christ G and Binder BR, 1987, Proliferation of a human epidermal tumor cell line by urokinase.FASEB Journal,1, 125–128.

    Google Scholar 

  76. Lyons RM, Keski-Oja J and Moses HL, 1988, Proteolytic activation of latent transforming growth factor-beta from fibroblast conditioned medium.Journal of Cell Biology,106, 1659–1665.

    Google Scholar 

  77. Ossowski L, Quigley JP and Reich E. Plasminogen-a necessary factor for cell migrationin vitro. In: Reich E, Rifkin DB, Shaw W, eds.Proteases and Biological Control. New York: Cold Spring Harbor Laboratory, 1975, pp. 901–913.

    Google Scholar 

  78. Gilbert LC and Gordon SG, 1983, Relationship between procoagulant activity and metastatic capacity of B16 mouse melanoma variants.Cancer Research,43, 536–540.

    Google Scholar 

  79. Day ED, Planinsek JA and Pressman D, 1959, Localisationin vivo of radioiodinated rat fibrinogen in the Murphy rat lymphosarcoma and in other transplantable rat tumors.Journal of the National Cancer Institute,22, 413–426.

    Google Scholar 

  80. Horn KV, Cavanaugh P and Evens C, 1982, Tumor cell-platelet aggregation: induced by cathepsin Blike proteinase and inhibited by prostacyclin.Science, 217, 540–542.

    Google Scholar 

  81. Sylven B, 1968, Cellular detachment by purified lysomal cathepsin B.European Journal of Cancer,4, 559–562.

    Google Scholar 

  82. Gross JL, Mosatelli D and Rifkin DB, 1983, Increased capillary endothelial protease activity in response to angiogenic stimuliin vitro.Proceedings of the National Academy of Sciences, USA,80, 2623–2627.

    Google Scholar 

  83. Gudewicz PW and Gilboa N, 1987, Human urokinase-type plasminogen activator stimulates chemotaxis of human neutrophils.Biochemistry and Biophysics Research Communications,147, 1176–1181.

    Google Scholar 

  84. Duffy MJ, O'Grady P, Devaney D, O'Siorain L, Fennelly JJand Lijnen HJ, 1988, Urokinase-plasminogen activator, a marker for aggressive breast cancers. Preliminary report.Cancer,62, 531–533.

    Google Scholar 

  85. Duffy MJ, Reilly D, O'Sullivan C, O'Higgins N, Fennelly JJ and Andreasen PA, 1990, Urokinase plasminogen activator, a new and independent prognostic marker in breast cancer.Cancer Research,50, 6827–6829.

    Google Scholar 

  86. Janicke F, Schmitt M, Hafter R, Holrieder A, Babic R, Ulm K, Gossner W and Graeff H, 1990, Urokinase-type plasminogen activator (u-PA) antigen is a predictor of early relapse in breast cancer.Fibrinolysis,4, 69–78.

    Google Scholar 

  87. Janicke F, Schmitt M, Ulm K, Gossner W and Graeff H, 1989, The urokinase-type plasminogen activator (u-PA) antigen is related to early relapse in breast cancer.Lancet,ii, 1049.

    Google Scholar 

  88. Duffy MJ, Reilly D, O'Sullivan C, O'Higgins N and Fennelly JJ, 1990, Urokinase plasminogen activator and prognosis in breast cancer.Lancet,335, 108.

    Google Scholar 

  89. Thorpe S, Rochefort H, Garcia M, Freiss G, Christensen IJ, Khalaf S, Paulucci F, Pau P, Rasmussen BB and Rose C, 1989, Association between high concentrations of Mr 52,000 cathepsin D and poor prognosis in primary human breast cancer.Cancer Research,49, 6008–6014.

    Google Scholar 

  90. Spyratos F, Brouillet JP, Defrenne A, Hacene K, Rouesse J, Maudelonde T, Brunet M, Andrieu C, Desplaces A and Rochefort H, 1989, Cathepsin D: an independent prognostic factor for metastasis of breast cancer.Lancet,ii, 1115–1118.

    Google Scholar 

  91. Tandon AK, Clarke GM, Chamness GC, Chirgwin J and McGuire WL, 1990, Cathepsin D and prognosis in breast cancer.New England Journal of Medicine,322, 297–302.

    Google Scholar 

  92. Henry JA, McCarthy AL, Angus B, Westley BR, May F, Nicholson S, Cairns J, Harris AL and Horne C, 1990, Prognostic significance of the estrogen regulated protein, cathepsin D, in breast cancer.Cancer,65, 265–271.

    Google Scholar 

  93. Daidone MG, Silvestrini R, D'Errico A, DiFronzo G, Benini E, Mancini AM, Garbisa S, Liotta L, Grigioni W, 1991, Laminin receptors, collagenase IV and prognosis in node negative breast cancer.International Journal of Cancer,48, 529–532.

    Google Scholar 

  94. Abramson M, Schilling RW, Huang C and Salome RG, 1975, Collagenase activity in epidermoid carcinoma of the oral cavity and larynx.Annals of Otololaryngology,84, 158–163.

    Google Scholar 

  95. Muller D, Breathnach R, Engelmann A, Millon R, Bronner G, Flesch H, Dumont P, Eber M and Abecassis J, 1991, Expression of collagenase-related metalloproteinase genes in human lung or head or neck tumours.International Journal of Cancer,48, 550–556.

    Google Scholar 

  96. Oka T, Ishida T, Nishino T and Sugimachi K, 1991, Immunohistochemical or urokinase-type plasminogen activator in primary and metastatic tumors of pulmonary adenocarcinoma.Cancer Research,51, 3522–3525.

    Google Scholar 

  97. Sappino A-P, Belin D, Huarte J, Hirschel-Scholz S, Saurat JH and Vassalli J-D, 1991, Differential protease expression by cutaneous squamous and basal cell carcinomas.Journal of Clinical Investigations,88, 1073–1079.

    Google Scholar 

  98. Duffy MJ, O'Grady P, Devaney D, O'Siorain L, Fennelly JJ and Lijnen R, 1988, Tissue-type plasminogen activator, a new prognostic marker in breast cancer.Cancer Research,48, 1348–1349.

    Google Scholar 

  99. Duffy MJ, O'Grady P, Simon J, Rose M and Lijnen HR, 1986, Tissue-type plasminogen activator in breast cancer: relationship with estradiol and progesterone receptors.Journal of the National Cancer Institute,77, 621–623.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Duffy, M.J. The role of proteolytic enzymes in cancer invasion and metastasis. Clin Exp Metast 10, 145–155 (1992). https://doi.org/10.1007/BF00132746

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00132746

Keywords

Navigation