Summary
Much progress has been made in understanding how matrix remodeling proteases, including metalloproteinases, serine proteases, and cysteine cathepsins, functionally contribute to cancer development. In addition to modulating extracellular matrix metabolism, proteases provide a significant protumor advantage to developing neoplasms through their ability to modulate bioavailability of growth and proangiogenic factors, regulation of bioactive chemokines and cytokines, and processing of cell–cell and cell–matrix adhesion molecules. Although some proteases directly regulate these events, it is now evident that some proteases indirectly contribute to cancer development by regulating posttranslational activation of latent zymogens that then directly impart regulatory information. Thus, many proteases act in a cascade-like manner and exert their functionality as part of a proteolytic pathway rather than simply functioning individually. Delineating the cascade of enzymatic activities contributing to overall proteolysis during carcinogenesis may identify rate-limiting steps or pathways that can be targeted with anti-cancer therapeutics. This chapter highlights recent insights into the complexity of roles played by pericellular and intracellular proteases by examining mechanistic studies as well as the roles of individual protease gene functions in various organ-specific mouse models of cancer development, with an emphasis on intersecting proteolytic activities that amplify programming of tissues to foster neoplastic development.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
1. Bissell, M. J., Aggeler, J. (1987) Dynamic reciprocity: how do extracellular matrix and hormones direct gene expression? Prog Clin Biol Res 249: 251–262.
2. Bissell, M. J., Radisky, D. (2001) Putting tumours in context. Nat Rev Cancer 1 (1): 46–54.
3. van Kempen, L. C., de Visser, K. E., Coussens, L. M. (2006) Inflammation, proteases and cancer. Eur J Cancer 42 (6): 728–734.
4. Blum, G., Mullins, S. R., Keren, K., et al (2005) Dynamic imaging of protease activity with fluorescently quenched activity-based probes. Nat Chem Biol 1 (4): 203–209.
5. Blum, G., von Degenfeld, G., Merchant, M. J., Blau, H. M., Bogyo, M. (2007) Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes. Nat Chem Biol 3 (10): 668–677.
6. Salomon, A. R., Ficarro, S. B., Brill, L. M., et al (2003) Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry. Proc Natl Acad Sci USA 100 (2): 443–448.
7.Sieber, S. A., Cravatt, B. F. (2006) Analytical platforms for activity-based protein profiling-exploiting the versatility of chemistry for functional proteomics. Chem Commun (Camb) (22): 2311–2319.
8. Sloane, B. F., Sameni, M., Podgorski, I., Cavallo-Medved, D., Moin, K. (2006) Functional imaging of tumor proteolysis. Annu Rev Pharmacol Toxicol 46: 301–315.
9. Kato, D., Boatright, K. M., Berger, A. B., et al (2005) Activity-based probes that target diverse cysteine protease families. Nat Chem Biol 1 (1): 33–38.
10. Lopez-Otin, C., Matrisian, L. M. (2007) Emerging roles of proteases in tumour suppression. Nat Rev Cancer 7 (10): 800–808.
11. Lopez-Otin, C., Overall, C. M. (2002) Protease degradomics: a new challenge for proteomics. Nat Rev Mol Cell Biol 3 (7): 509–519.
12. Hoffman, M. M., Monroe, D. M. (2005) Rethinking the coagulation cascade. Curr Hematol Rep 4 (5): 391–396.
13. Carroll, M. C. (2004) The complement system in regulation of adaptive immunity. Nat Immunol 5 (10): 981–986.
14. Egeblad, M., Werb, Z. (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2: 161–174.
15. Puente, X. S., Pendás, A. M., Llano, E., Velasco, G., López-Otín, C. (1996) Molecular cloning of a novel membrane-type matrix metalloproteinase from a human breast carcinoma. Cancer Res 56 (5): 944–949.
16. Rhee, J. S., Coussens, L. M. (2002) RECKing MMP function: implications for cancer development. Trends Cell Biol 12 (5): 209–211.
17. Frank, B. T., Rossall, J. C., Caughey, G. H., Fang, K. C. (2001) Mast cell tissue inhibitor of metalloproteinase-1 is cleaved and inactivated extracellularly by alpha-chymase. J Immunol 166 (4): 2783–2792.
18. Coussens, L. M., Hanahan, D., Arbeit, J. M. (1996) Genetic predisposition and parameters of malignant progression in K14-HPV16 transgenic mice. Am J Path 149 (6): 1899–1917.
19. Coussens, L. M., Tinkle, C. L., Hanahan, D., Werb, Z. (2000) MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 103 (3): 481–490.
20. Bergers, G., Brekken, R., McMahon, G., et al (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2 (10): 737–744.
21. Giraudo, E., Inoue, M., Hanahan, D. (2004) An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest 114 (5): 623–633.
22. Huang, S., Van Arsdall, M., Tedjarati, S., et al (2002) Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice. J.Natl.Cancer Inst. 94 (15): 1134–1142.
23. Jodele, S., Chantrain, C. F., Blavier, L., et al (2005) The contribution of bone marrow-derived cells to the tumor vasculature in neuroblastoma is matrix metalloproteinase-9 dependent. Cancer Res 65 (8): 3200–3208.
24. D’Armiento, J., DiColandrea, T., Dalal, S. S., et al (1995) Collagenase expression in transgenic mouse skin causes hyperkeratosis and acanthosis and increases susceptibility to tumorigenesis. Mol Cell Biol 15 (10): 5732–5739.
25. Masson, R., Lefebvre, O., Noel, A., et al (1998) In vivo evidence that the stromelysin-3 metalloproteinase contributes in a paracrine manner to epithelial cell malignancy. J.Cell Biol 140 (6): 1535–1541.
26. Wilson, C. L., Heppner, K. J., Labosky, P. A., Hogan, B. L., Matrisian, L. M. (1997) Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci USA 94 (4): 1402–1407.
27. Sternlicht, M. D., Lochter, A., Sympson, C. J., et al (1999) The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell 98 (2): 137–146.
28. Rudolph-Owen, L. A., Cannon, P., Matrisian, L. M. (1998) Overexpression of the matrix metalloproteinase matrilysin results in premature mammary gland differentiation and male infertility. Mol Biol Cell 9 (2): 421–435.
29. Ha, H. Y., Moon, H. B., Nam, M. S., et al (2001) Overexpression of membrane-type matrix metalloproteinase-1 gene induces mammary gland abnormalities and adenocarcinoma in transgenic mice. Cancer Res 61 (3): 984–990.
30. McCawley, L. J., Crawford, H. C., King, L. E., Jr., Mudgett, J., Matrisian, L. M. (2004) A protective role for matrix metalloproteinase-3 in squamous cell carcinoma. Cancer Res 64 (19): 6965–6972.
31. Balbin, M., Fueyo, A., Tester, A. M., et al (2003) Loss of collagenase-2 confers increased skin tumor susceptibility to male mice. Nat Genet 35 (3): 252–257.
32. Martin, D. C., Rüther, U., Sanchez-Sweatman, O. H., Orr, F. W., Khokha, R. (1996) Inhibition of SV40 T antigen-induced hepatocellular carcinoma in TIMP-1 transgenic mice. Oncogene 13 (3): 569–576.
33. Buck, T. B., Yoshiji, H., Harris, S. R., Bunce, O. R., Thorgeirsson, U. P. (1999) The effects of sustained elevated levels of circulating tissue inhibitor of metalloproteinases-1 on the development of breast cancer in mice. Ann N Y Acad Sci 878: 732–735.
34. Rhee, J. S., Diaz, R., Korets, L., Hodgson, J. G., Coussens, L. M. (2004) TIMP-1 Alters Susceptibility to Carcinogenesis. Cancer Res 64 (3): 952–961.
35. Kopitz, C., Gerg, M., Bandapalli, O. R., et al (2007) Tissue inhibitor of metalloproteinases-1 promotes liver metastasis by induction of hepatocyte growth factor signaling. Cancer Res 67 (18): 8615–8623.
36. Itoh, Y., Takamura, A., Ito, N., et al (2001) Homophilic complex formation of MT1-MMP facilitates proMMP-2 activation on the cell surface and promotes tumor cell invasion. Embo J 20 (17): 4782–4793.
37. Wang, Z., Juttermann, R., Soloway, P. D. (2000) TIMP-2 is required for efficient activation of proMMP-2 in vivo. J Biol Chem 275 (34): 26411–26415.
38. Worley, J. R., Thompkins, P. B., Lee, M. H., et al (2003) Sequence motifs of tissue inhibitor of metalloproteinases 2 (TIMP-2) determining progelatinase A (proMMP-2) binding and activation by membrane-type metalloproteinase 1 (MT1-MMP). Biochem J 372 (Pt 3): 799–809.
39. Bergers, G., Coussens, L. M. (2000) Extrinsic regulators of epithelial tumor progression: metalloproteinases. Curr Opin Genet Dev 10 (1): 120–127.
40. Chantrain, C. F., Henriet, P., Jodele, S., et al (2006) Mechanisms of pericyte recruitment in tumour angiogenesis: a new role for metalloproteinases. Eur J Cancer 42 (3): 310–318.
41. Chantrain, C., Shimada, H., Jodele, S., et al (2004) Stromal matrix metalloproteinase-9 regulates the vascular architecture in neuroblastoma by promoting pericyte recruitment. Cancer Res 64: 1675–1686.
42. Heissig, B., Hattori, K., Dias, S., et al (2002) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 109 (5): 625–637.
43. Acuff, H. B., Carter, K. J., Fingleton, B., Gorden, D. L., Matrisian, L. M. (2006) Matrix metalloproteinase-9 from bone marrow-derived cells contributes to survival but not growth of tumor cells in the lung microenvironment. Cancer Res 66 (1): 259–266.
44. Hiratsuka, S., Nakamura, K., Iwai, S., et al (2002) MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer Cell 2 (4): 289–300.
45. Giannelli, G., Falk-Marzillier, J., Schiraldi, O., Stetler-Stevenson, W. G., Quaranta, V. (1997) Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. Science 277 (5323): 225–228.
46. Koshikawa, N., Giannelli, G., Cirulli, V., Miyazaki, K., Quaranta, V. (2000) Role of cell surface metalloprotease MT1-MMP in epithelial cell migration over laminin-5. J Cell Biol 148 (3): 615–624.
47. Lochter, A., Galosy, S., Muschler, J., Freedman, N., Werb, Z., Bissell, M. J. (1997) Matrix metalloproteinase stromelysin-1 triggers a cascade of molecular alterations that leads to stable epithelial-to-mesenchymal conversion and a premalignant phenotype in mammary epithelial cells. J Cell Biol 139 (7): 1861–1872.
48. Coussens, L. M., Fingleton, B., Matrisian, L. M. (2002) Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295 (5564): 2387–2392.
49. Blobel, C. P. (2005) ADAMs: key components in EGFR signalling and development. Nat Rev Mol Cell Biol 6 (1): 32–43.
50. Killar, L., White, J., Black, R., Peschon, J. (1999) Adamalysins. A family of metzincins including TNF-alpha converting enzyme (TACE). Ann N Y Acad Sci 878: 442–452.
51. White, J. M. (2003) ADAMs: modulators of cell-cell and cell-matrix interactions. Curr Opin Cell Biol 15 (5): 598–606.
52. Howard, L., Lu, X., Mitchell, S., Griffiths, S., Glynn, P. (1996) Molecular cloning of MADM: a catalytically active mammalian disintegrin-metalloprotease expressed in various cell types. Biochem J 317 (Pt 1): 45–50.
53. Howard, L., Zheng, Y., Horrocks, M., Maciewicz, R. A., Blobel, C. (2001) Catalytic activity of ADAM28. FEBS Lett 498 (1): 82–86.
54. Loechel, F., Gilpin, B. J., Engvall, E., Albrechtsen, R., Wewer, U. M. (1998) Human ADAM 12 (meltrin alpha) is an active metalloprotease. J Biol Chem 273 (27): 16993–16997.
55. Moss, M. L., Jin, S. L., Milla, M. E., et al (1997) Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature 385 (6618): 733–736.
56. Carl-McGrath, S., Lendeckel, U., Ebert, M., Roessner, A., Rocken, C. (2005) The disintegrin-metalloproteinases ADAM9, ADAM12, and ADAM15 are upregulated in gastric cancer. Int J Oncol 26 (1): 17–24.
57. Le Pabic, H., Bonnier, D., Wewer, U. M., et al (2003) ADAM12 in human liver cancers: TGF-beta-regulated expression in stellate cells is associated with matrix remodeling. Hepatology 37 (5): 1056–1066.
58. Lendeckel, U., Kohl, J., Arndt, M., Carl-McGrath, S., Donat, H., Rocken, C. (2005) Increased expression of ADAM family members in human breast cancer and breast cancer cell lines. J Cancer Res Clin Oncol 131 (1): 41–48.
59. Peduto, L., Reuter, V. E., Shaffer, D. R., Scher, H. I., Blobel, C. P. (2005) Critical function for ADAM9 in mouse prostate cancer. Cancer Res 65 (20): 9312–9319.
60. Roy, R., Wewer, U. M., Zurakowski, D., Pories, S. E., Moses, M. A. (2004) ADAM 12 cleaves extracellular matrix proteins and correlates with cancer status and stage. J Biol Chem 279 (49): 51323–51330.
61. Wu, E., Croucher, P. I., McKie, N. (1997) Expression of members of the novel membrane linked metalloproteinase family ADAM in cells derived from a range of haematological malignancies. Biochem Biophys Res Commun 235 (2): 437–442.
62. Zheng, X., Jiang, F., Katakowski, M., et al (2007) Inhibition of ADAM17 reduces hypoxia-induced brain tumor cell invasiveness. Cancer Sci 98 (5): 674–684.
63. Zhou, B. B., Peyton, M., He, B., et al (2006) Targeting ADAM-mediated ligand cleavage to inhibit HER3 and EGFR pathways in non-small cell lung cancer. Cancer Cell 10 (1): 39–50.
64. Kenny, P. A., Bissell, M. J. (2007) Targeting TACE-dependent EGFR ligand shedding in breast cancer. J Clin Invest 117 (2): 337–345.
65. Evangelou, A. I., Winter, S. F., Huss, W. J., Bok, R. A., Greenberg, N. M. (2004) Steroid hormones, polypeptide growth factors, hormone refractory prostate cancer, and the neuroendocrine phenotype. J Cell Biochem 91 (4): 671–683.
66. Mimeault, M., Batra, S. K. (2006) Recent advances on multiple tumorigenic cascades involved in prostatic cancer progression and targeting therapies. Carcinogenesis 27 (1): 1–22.
67. Peduto, L., Reuter, V. E., Sehara-Fujisawa, A., Shaffer, D. R., Scher, H. I., Blobel, C. P. (2006) ADAM12 is highly expressed in carcinoma-associated stroma and is required for mouse prostate tumor progression. Oncogene 25 (39): 5462–5466.
68. Kveiborg, M., Frohlich, C., Albrechtsen, R., et al (2005) A role for ADAM12 in breast tumor progression and stromal cell apoptosis. Cancer Res 65 (11): 4754–4761.
69. Ringel, J., Jesnowski, R., Moniaux, N., et al (2006) Aberrant expression of a disintegrin and metalloproteinase 17/tumor necrosis factor-alpha converting enzyme increases the malignant potential in human pancreatic ductal adenocarcinoma. Cancer Res 66 (18): 9045–9053.
70. Martin, J., Eynstone, L. V., Davies, M., Williams, J. D., Steadman, R. (2002) The role of ADAM 15 in glomerular mesangial cell migration. J Biol Chem 277 (37): 33683–33689.
71. Millichip, M. I., Dallas, D. J., Wu, E., Dale, S., McKie, N. (1998) The metallo-disintegrin ADAM10 (MADM) from bovine kidney has type IV collagenase activity in vitro. Biochem Biophys Res Commun 245 (2): 594–598.
72. Alfandari, D., Cousin, H., Gaultier, A., et al (2001) Xenopus ADAM 13 is a metalloprotease required for cranial neural crest-cell migration. Curr Biol 11 (12): 918–930.
73. Horiuchi, K., Weskamp, G., Lum, L., et al (2003) Potential role for ADAM15 in pathological neovascularization in mice. Mol Cell Biol 23 (16): 5614–5624.
74. Herren, B., Raines, E. W., Ross, R. (1997) Expression of a disintegrin-like protein in cultured human vascular cells and in vivo. Faseb J 11 (2): 173–180.
75. Trochon, V., Li, H., Vasse, M., et al (1998) Endothelial metalloprotease-disintegrin protein (ADAM) is implicated in angiogenesis in vitro. Angiogenesis 2 (3): 277–285.
76. Yarden, Y., Sliwkowski, M. X. (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2 (2): 127–137.
77. Borrell-Pages, M., Rojo, F., Albanell, J., Baselga, J., Arribas, J. (2003) TACE is required for the activation of the EGFR by TGF-alpha in tumors. Embo J 22 (5): 1114–1124.
78. Giaccone, G., Herbst, R. S., Manegold, C., et al (2004) Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1. J Clin Oncol 22 (5): 777–784.
79. Herbst, R. S., Giaccone, G., Schiller, J. H., et al (2004) Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2. J Clin Oncol 22 (5): 785–794.
80. Herbst, R. S., Sandler, A. B. (2004) Overview of the current status of human epidermal growth factor receptor inhibitors in lung cancer. Clin Lung Cancer 6 Suppl 1: S7–S19.
81. Huovila, A. P., Turner, A. J., Pelto-Huikko, M., Karkkainen, I., Ortiz, R. M. (2005) Shedding light on ADAM metalloproteinases. Trends Biochem Sci 30 (7): 413–422.
82. Mohammed, F. F., Smookler, D. S., Taylor, S. E., et al (2004) Abnormal TNF activity in Timp3-/- mice leads to chronic hepatic inflammation and failure of liver regeneration. Nat Genet 36 (9): 969–977.
83. Toth, M., Sohail, A., Mobashery, S., Fridman, R. (2006) MT1-MMP shedding involves an ADAM and is independent of its localization in lipid rafts. Biochem Biophys Res Commun 350 (2): 377–384.
84. Osenkowski, P., Toth, M., Fridman, R. (2004) Processing, shedding, and endocytosis of membrane type 1-matrix metalloproteinase (MT1-MMP). J Cell Physiol 200 (1): 2–10.
85. Bugge, T. H., Lund, L. R., Kombrinck, K. K., et al (1998) Reduced metastasis of Polyoma virus middle T antigen-induced mammary cancer in plasminogen-deficient mice. Oncogene 16 (24): 3097–3104.
86. Coussens, L. M., Raymond, W. W., Bergers, G., et al (1999) Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev 13 (11): 1382–1397.
87. Starcher, B., O’Neal, P., Granstein, R. D., Beissert, S. (1996) Inhibition of neutrophil elastase suppresses the development of skin tumors in hairless mice. J Invest Dermatol 107 (2): 159–163.
88. Netzel-Arnett, S., Hooper, J. D., Szabo, R., et al (2003) Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer. Cancer Metastasis Rev 22 (2–3): 237–258.
89. Caughey, G. H. (2002) New developments in the genetics and activation of mast cell proteases. Mol Immunol 38 (16–18): 1353–1357.
90. Reiling, K. K., Krucinski, J., Miercke, L. J., Raymond, W. W., Caughey, G. H., Stroud, R. M. (2003) Structure of human pro-chymase: a model for the activating transition of granule-associated proteases. Biochemistry 42 (9): 2616–2624.
91. Ramos-DeSimone, N., Hahn-Dantona, E., Sipley, J., Nagase, H., French, D. L., Quigley, J. P. (1999) Activation of matrix metalloproteinase-9 (MMP-9) via a converging plasmin/stromelysin-1 cascade enhances tumor cell invasion. J Biol Chem 274 (19): 13066–13076.
92. Pollanen, J., Hedman, K., Nielsen, L. S., Dano, K., Vaheri, A. (1988) Ultrastructural localization of plasma membrane-associated urokinase-type plasminogen activator at focal contacts. J Cell Biol 106 (1): 87–95.
93. Ellis, V., Behrendt, N., Dano, K. (1991) Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor. J Biol Chem 266 (19): 12752–12758.
94. Wun, T. C., Reich, E. (1987) An inhibitor of plasminogen activation from human placenta. Purification and characterization. J Biol Chem 262 (8): 3646–3653.
95. Conese, M., Blasi, F. (1995) Urokinase/urokinase receptor system: internalization/degradation of urokinase-serpin complexes: mechanism and regulation. Biol Chem Hoppe Seyler 376 (3): 143–155.
96. Ploplis, V., Tipton, H., Menchen, H., Castellino, F. (2007) A urokinase-type plasminogen activator deficiency diminishes the frequency of intestinal adenomas in Apc(Min/+) mice. J Pathol 213 (3): 266–274.
97. Ploplis, V. A. (2001) Gene targeting in hemostasis. plasminogen. Front Biosci 6: D555–D569.
98. Hahn-Dantona, E., Ramos-DeSimone, N., Sipley, J., Nagase, H., French, D. L., Quigley, J. P. (1999) Activation of proMMP-9 by a plasmin/MMP-3 cascade in a tumor cell model. Regulation by tissue inhibitors of metalloproteinases. Ann N Y Acad Sci 878: 372–387.
99. He, C. S., Wilhelm, S. M., Pentland, A. P., et al (1989) Tissue cooperation in a proteolytic cascade activating human interstitial collagenase. Proc Natl Acad Sci USA 86 (8): 2632–2636.
100. Monea, S., Lehti, K., Keski-Oja, J., Mignatti, P. (2002) Plasmin activates pro-matrix metalloproteinase-2 with a membrane-type 1 matrix metalloproteinase-dependent mechanism. J Cell Physiol 192 (2): 160–170.
101. Blank, U., Rivera, J. (2004) The ins and outs of IgE-dependent mast-cell exocytosis. Trends Immunol 25 (5): 266–273.
102. el-Lati, S. G., Dahinden, C. A., Church, M. K. (1994) Complement peptides C3a- and C5a-induced mediator release from dissociated human skin mast cells. J Invest Dermatol 102 (5): 803–806.
103. Karimi, K., Redegeld, F. A., Blom, R., Nijkamp, F. P. (2000) Stem cell factor and interleukin-4 increase responsiveness of mast cells to substance P. Exp Hematol 28 (6): 626–634.
104. Hogaboam, C., Kunkel, S. L., Strieter, R. M., et al (1998) Novel role of transmembrane SCF for mast cell activation and eotaxin production in mast cell-fibroblast interactions. J Immunol 160 (12): 6166–6171.
105. Kulka, M., Alexopoulou, L., Flavell, R. A., Metcalfe, D. D. (2004) Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3. J Allergy Clin Immunol 114 (1): 174–182.
106. Tchougounova, E., Pejler, G., Abrink, M. (2003) The chymase, mouse mast cell protease 4, constitutes the major chymotrypsin-like activity in peritoneum and ear tissue. A role for mouse mast cell protease 4 in thrombin regulation and fibronectin turnover. J Exp Med 198 (3): 423–431.
107. Tchougounova, E., Lundequist, A., Fajardo, I., Winberg, J. O., Abrink, M., Pejler, G. (2005) A key role for mast cell chymase in the activation of pro-matrix metalloprotease-9 and pro-matrix metalloprotease-2. J Biol Chem 280 (10): 9291–9296.
108. Ghildyal, N., Friend, D. S., Stevens, R. L., et al (1996) Fate of two mast cell tryptases in V3 mastocytosis and normal BALB/c mice undergoing passive systemic anaphylaxis: prolonged retention of exocytosed mMCP-6 in connective tissues, and rapid accumulation of enzymatically active mMCP-7 in the blood. J Exp Med 184 (3): 1061–1073.
109. Wong, G. W., Yasuda, S., Morokawa, N., Li, L., Stevens, R. L. (2004) Mouse chromosome 17A3.3 contains 13 genes that encode functional tryptic-like serine proteases with distinct tissue and cell expression patterns. J Biol Chem 279 (4): 2438–2452.
110. Caughey, G. H. (2007) Mast cell tryptases and chymases in inflammation and host defense. Immunol Rev 217: 141–154.
111. Schechter, I., Berger, A. (1967) On the size of the active site in proteases. I. Papain. Biochem Biophys Res Commun 27 (2): 157–162.
112. Schechter, N. M., Choi, J. K., Slavin, D. A., et al (1986) Identification of a chymotrypsin-like proteinase in human mast cells. J Immunol 137 (3): 962–970.
113. He, S., Walls, A. F. (1998) Human mast cell chymase induces the accumulation of neutrophils, eosinophils and other inflammatory cells in vivo. Br J Pharmacol 125 (7): 1491–1500.
114. Gruber, B. L., Marchese, M. J., Suzuki, K., et al (1989) Synovial procollagenase activation by human mast cell tryptase dependence upon matrix metalloproteinase 3 activation. J Clin Invest 84 (5): 1657–1662.
115. Hartmann, T., Ruoss, S. J., Raymond, W. W., Seuwen, K., Caughey, G. H. (1992) Human tryptase as a potent, cell-specific mitogen: role of signaling pathways in synergistic responses. Am J Physiol 262 (5 Pt 1): L528–L534.
116. Ruoss, S. J., Hartmann, T., Caughey, G. H. (1991) Mast cell tryptase is a mitogen for cultured fibroblasts. J Clin Invest 88 (2): 493–499.
117. Cairns, J. A., Walls, A. F. (1996) Mast cell tryptase is a mitogen for epithelial cells. Stimulation of IL-8 production and intercellular adhesion molecule-1 expression. J Immunol 156 (1): 275–283.
118. Huang, C., Friend, D. S., Qiu, W. T., et al (1998) Induction of a selective and persistent extravasation of neutrophils into the peritoneal cavity by tryptase mouse mast cell protease 6. J Immunol 160 (4): 1910–1919.
119. Compton, S. J., Cairns, J. A., Holgate, S. T., Walls, A. F. (1999) Interaction of human mast cell tryptase with endothelial cells to stimulate inflammatory cell recruitment. Int Arch Allergy Immunol 118 (2–4): 204–205.
120. Wolters, P. J., Pham, C. T., Muilenburg, D. J., Ley, T. J., Caughey, G. H. (2001) Dipeptidyl peptidase I is essential for activation of mast cell chymases, but not tryptases, in mice. J Biol Chem 276 (21): 18551–18566.
121. Fouret, P., du Bois, R. M., Bernaudin, J. F., Takahashi, H., Ferrans, V. J., Crystal, R. G. (1989) Expression of the neutrophil elastase gene during human bone marrow cell differentiation. J Exp Med 169 (3): 833–845.
122. Zimmer, M., Medcalf, R. L., Fink, T. M., Mattmann, C., Lichter, P., Jenne, D. E. (1992) Three human elastase-like genes coordinately expressed in the myelomonocyte lineage are organized as a single genetic locus on 19pter. Proc Natl Acad Sci USA 89 (17): 8215–8219.
123. Chua, F., Laurent, G. J. (2006) Neutrophil elastase: mediator of extracellular matrix destruction and accumulation. Proc Am Thorac Soc 3 (5): 424–427.
124. Akizuki, M., Fukutomi, T., Takasugi, M., et al (2007) Prognostic significance of immunoreactive neutrophil elastase in human breast cancer: long-term follow-up results in 313 patients. Neoplasia 9 (3): 260–264.
125. Yamashita, J., Tashiro, K., Yoneda, S., Kawahara, K., Shirakusa, T. (1996) Local increase in polymorphonuclear leukocyte elastase is associated with tumor invasiveness in non-small cell lung cancer. Chest 109 (5): 1328–1334.
126. Lane, A., Ley, T. J. (2003) Neutrophil elastase cleaves PML-RARalpha and is important for the development of acute promyelocytic leukemia in mice. Cell 1115: 305–318.
127. Ferry, G., Lonchampt, M., Pennel, L., de Nanteuil, G., Canet, E., Tucker, G. C. (1997) Activation of MMP-9 by neutrophil elastase in an in vivo model of acute lung injury. FEBS Lett 402 (2–3): 111–115.
128. Nakamura, H., Yoshimura, K., McElvaney, N. G., Crystal, R. G. (1992) Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line. J Clin Invest 89 (5): 1478–1484.
129. Cepinskas, G., Sandig, M., Kvietys, P. R. (1999) PAF-induced elastase-dependent neutrophil transendothelial migration is associated with the mobilization of elastase to the neutrophil surface and localization to the migrating front. J Cell Sci 112 (Pt 12): 1937–1945.
130. Belaaouaj, A., McCarthy, R., Baumann, M., et al (1998) Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nat Med 4 (5): 615–618.
131. Brinkmann, V., Reichard, U., Goosmann, C., et al (2004) Neutrophil extracellular traps kill bacteria. Science 303 (5663): 1532–1535.
132. Young, R. E., Voisin, M. B., Wang, S., Dangerfield, J., Nourshargh, S. (2007) Role of neutrophil elastase in LTB(4)-induced neutrophil transmigration in vivo assessed with a specific inhibitor and neutrophil elastase deficient mice. Br J Pharmacol 151 (5): 628–637.
133. Woodman, R. C., Reinhardt, P. H., Kanwar, S., Johnston, F. L., Kubes, P. (1993) Effects of human neutrophil elastase (HNE) on neutrophil function in vitro and in inflamed microvessels. Blood 82 (7): 2188–2195.
134. Sato, T., Takahashi, S., Mizumoto, T., et al (2006) Neutrophil elastase and cancer. Surg Oncol 15 (4): 217–222.
135. Nozawa, F., Hirota, M., Okabe, A., et al (2000) Elastase activity enhances the adhesion of neutrophil and cancer cells to vascular endothelial cells. J Surg Res 94 (2): 153–158.
136. Hirche, T. O., Atkinson, J. J., Bahr, S., Belaaouaj, A. (2004) Deficiency in neutrophil elastase does not impair neutrophil recruitment to inflamed sites. Am J Respir Cell Mol Biol 30 (4): 576–584.
137. Young, R. E., Thompson, R. D., Larbi, K. Y., et al (2004) Neutrophil elastase (NE)-deficient mice demonstrate a nonredundant role for NE in neutrophil migration, generation of proinflammatory mediators, and phagocytosis in response to zymosan particles in vivo. J Immunol 172 (7): 4493–4502.
138. Baugh, R. J., Travis, J. (1976) Human leukocyte granule elastase: rapid isolation and characterization. Biochemistry 15 (4): 836–841.
139. McDonald, J. A., Kelley, D. G. (1980) Degradation of fibronectin by human leukocyte elastase. Release of biologically active fragments. J Biol Chem 255 (18): 8848–8858.
140. Mainardi, C. L., Dixit, S. N., Kang, A. H. (1980) Degradation of type IV (basement membrane) collagen by a proteinase isolated from human polymorphonuclear leukocyte granules. J Biol Chem 255 (11): 5435–5441.
141. Shamamian, P., Schwartz, J. D., Pocock, B. J., et al (2001) Activation of progelatinase A (MMP-2) by neutrophil elastase, cathepsin G, and proteinase-3: a role for inflammatory cells in tumor invasion and angiogenesis. J Cell Physiol 189 (2): 197–206.
142. Okada, Y., Nakanishi, I. (1989) Activation of matrix metalloproteinase 3 (stromelysin) and matrix metalloproteinase 2 (‘gelatinase’) by human neutrophil elastase and cathepsin G. FEBS Lett. 249 (2): 353–356.
143. Liu, Z., Zhou, X., Shapiro, S. D., et al (2000) The serpin alpha1-proteinase inhibitor is a critical substrate for gelatinase B/MMP-9 in vivo. Cell 102 (5): 647–655.
144. Adkison, A. M., Raptis, S. Z., Kelley, D. G., Pham, C. T. (2002) Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute experimental arthritis. J Clin Invest 109 (3): 363–371.
145. Owen, C. A., Campbell, M. A., Sannes, P. L., Boukedes, S. S., Campbell, E. J. (1995) Cell surface-bound elastase and cathepsin G on human neutrophils: a novel, non-oxidative mechanism by which neutrophils focus and preserve catalytic activity of serine proteinases. J Cell Biol 131 (3): 775–789.
146. Lee, W. L., Downey, G. P. (2001) Leukocyte elastase: physiological functions and role in acute lung injury. Am J Respir Crit Care Med 164 (5): 896–904.
147. Matrisian, L. M. (1999) Cancer biology: extracellular proteinases in malignancy. Curr Biol 9 (20): R776–R778.
148. List, K., Bugge, T. H., Szabo, R. (2006) Matriptase: potent proteolysis on the cell surface. Mol Med 12 (1–3): 1–7.
149. Mok, S. C., Chao, J., Skates, S., et al (2001) Prostasin, a potential serum marker for ovarian cancer: identification through microarray technology. J Natl Cancer Inst 93 (19): 1458–1464.
150. List, K., Szabo, R., Molinolo, A., et al (2005) Deregulated matriptase causes ras-independent multistage carcinogenesis and promotes ras-mediated malignant transformation. Genes Dev 19 (16): 1934–1950.
151. Klezovitch, O., Chevillet, J., Mirosevich, J., Roberts, R. L., Matusik, R. J., Vasioukhin, V. (2004) Hepsin promotes prostate cancer progression and metastasis. Cancer Cell 6 (2): 185–195.
152. Moran, P., Li, W., Fan, B., Vij, R., Eigenbrot, C., Kirchhofer, D. (2006) Pro-urokinase-type plasminogen activator is a substrate for hepsin. J Biol Chem 281 (41): 30439–30446.
153. Suzuki, M., Kobayashi, H., Kanayama, N., et al (2004) Inhibition of tumor invasion by genomic down-regulation of matriptase through suppression of activation of receptor-bound pro-urokinase. J Biol Chem 279 (15): 14899–14908.
154. Jin, X., Yagi, M., Akiyama, N., et al (2006) Matriptase activates stromelysin (MMP-3) and promotes tumor growth and angiogenesis. Cancer Sci 97 (12): 1327–1334.
155. Turk, D., Janjic, V., Stern, I., et al (2001) Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases. Embo J 20 (23): 6570–6582.
156. Turk, V., Turk, B., Guncar, G., Turk, D., Kos, J. (2002) Lysosomal cathepsins: structure, role in antigen processing and presentation, and cancer. Adv Enzyme Regul 42: 285–303.
157. McGuire, M. J., Lipsky, P. E., Thiele, D. L. (1992) Purification and characterization of dipeptidyl peptidase I from human spleen. Arch Biochem Biophys 295 (2): 280–288.
158. Hallgren, J., Pejler, G. (2006) Biology of mast cell tryptase. An inflammatory mediator. Febs J 273 (9): 1871–1895.
159. Vasiljeva, O., Reinheckel, T., Peters, C., Turk, D., Turk, V., Turk, B. (2007) Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Curr Pharm Des 13 (4): 387–403.
160. Dolenc, I., Turk, B., Pungercic, G., Ritonja, A., Turk, V. (1995) Oligomeric structure and substrate induced inhibition of human cathepsin C. J Biol Chem 270 (37): 21626–21631.
161. Cigic, B., Dahl, S. W., Pain, R. H. (2000) The residual pro-part of cathepsin C fulfills the criteria required for an intramolecular chaperone in folding and stabilizing the human proenzyme. Biochemistry 39 (40): 12382–12390.
162. Dahl, S. W., Halkier, T., Lauritzen, C., et al (2001) Human recombinant pro-dipeptidyl peptidase I (cathepsin C) can be activated by cathepsins L and S but not by autocatalytic processing. Biochemistry 40 (6): 1671–1678.
163. Shresta, S., Pham, C. T., Thomas, D. A., Graubert, T. A., Ley, T. J. (1998) How do cytotoxic lymphocytes kill their targets? Curr Opin Immunol 10 (5): 581–587.
164. Mallen-St Clair, J., Pham, C. T., Villalta, S. A., Caughey, G. H., Wolters, P. J. (2004) Mast cell dipeptidyl peptidase I mediates survival from sepsis. J Clin Invest 113 (4): 628–634.
165. Gocheva, V., Zeng, W., Ke, D., et al (2006) Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev 20 (5): 543–556.
166. Joyce, J. A., Baruch, A., Chehade, K., et al (2004) Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 5 (5): 443–453.
167. Guy, C. T., Cardiff, R. D., Muller, W. J. (1992) Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol Cell Biol 12 (3): 954–961.
168. Vasiljeva, O., Papazoglou, A., Kruger, A., et al (2006) Tumor cell-derived and macrophage-derived cathepsin B promotes progression and lung metastasis of mammary cancer. Cancer Res 66 (10): 5242–5250.
169. de Haar, S. F., Jansen, D. C., Schoenmaker, T., De Vree, H., Everts, V., Beertsen, W. (2004) Loss-of-function mutations in cathepsin C in two families with Papillon-Lefevre syndrome are associated with deficiency of serine proteinases in PMNs. Hum Mutat 23 (5): 524.
170. Frezzini, C., Leao, J. C., Porter, S. (2004) Cathepsin C involvement in the aetiology of Papillon-Lefevre syndrome. Int J Paediatr Dent 14 (6): 466–467.
171. Hewitt, C., McCormick, D., Linden, G., et al (2004) The role of cathepsin C in Papillon-Lefevre syndrome, prepubertal periodontitis, and aggressive periodontitis. Hum Mutat 23 (3): 222–228.
172. Noack, B., Gorgens, H., Hoffmann, T., et al (2004) Novel mutations in the cathepsin C gene in patients with pre-pubertal aggressive periodontitis and Papillon-Lefevre syndrome. J Dent Res 83 (5): 368–370.
173. Pham, C. T., Ivanovich, J. L., Raptis, S. Z., Zehnbauer, B., Ley, T. J. (2004) Papillon-Lefevre syndrome: correlating the molecular, cellular, and clinical consequences of cathepsin C/dipeptidyl peptidase I deficiency in humans. J Immunol 173 (12): 7277–7281.
174. Pham, C. T., Ley, T. J. (1999) Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo. Proc Natl Acad Sci USA 96 (15): 8627–8632.
175. Sheth, P. D., Pedersen, J., Walls, A. F., McEuen, A. R. (2003) Inhibition of dipeptidyl peptidase I in the human mast cell line HMC-1: blocked activation of tryptase, but not of the predominant chymotryptic activity. Biochem Pharmacol 66 (11): 2251–2262.
176. Sakai, K., Ren, S., Schwartz, L. B. (1996) A novel heparin-dependent processing pathway for human tryptase. Autocatalysis followed by activation with dipeptidyl peptidase I. J Clin Invest 97 (4): 988–995.
177. Overall, C. M., Kleifeld, O. (2006) Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat Rev Cancer 6 (3): 227–239.
178. Bell-McGuinn, K. M., Garfall, A. L., Bogyo, M., Hanahan, D., Joyce, J. A. (2007) Inhibition of cysteine cathepsin protease activity enhances chemotherapy regimens by decreasing tumor growth and invasiveness in a mouse model of multistage cancer. Cancer Res 67 (15): 7378–7385.
179. Lakka, S. S., Gondi, C. S., Yanamandra, N., et al (2004) Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis. Oncogene 23 (27): 4681–4689.
180. Lakka, S. S., Gondi, C. S., Dinh, D. H., et al (2005) Specific interference of urokinase-type plasminogen activator receptor and matrix metalloproteinase-9 gene expression induced by double-stranded RNA results in decreased invasion, tumor growth, and angiogenesis in gliomas. J Biol Chem 280 (23): 21882–21892.
181. Lakka, S. S., Gondi, C. S., Yanamandra, N., et al (2003) Synergistic down-regulation of urokinase plasminogen activator receptor and matrix metalloproteinase-9 in SNB19 glioblastoma cells efficiently inhibits glioma cell invasion, angiogenesis, and tumor growth. Cancer Res 63 (10): 2454–2461.
182. Devy, L., de Groot, F. M., Blacher, S., et al (2004) Plasmin-activated doxorubicin prodrugs containing a spacer reduce tumor growth and angiogenesis without systemic toxicity. Faseb J 18 (3): 565–567.
183. Panchal, R. G., Cusack, E., Cheley, S., Bayley, H. (1996) Tumor protease-activated, pore-forming toxins from a combinatorial library. Nat Biotechnol 14 (7): 852–856.
184. Caldas, H., Jaynes, F. O., Boyer, M. W., Hammond, S., Altura, R. A. (2006) Survivin and Granzyme B-induced apoptosis, a novel anticancer therapy. Mol Cancer Ther 5 (3): 693–703.
185.Jodele, S., Chantrain C. F., Blavier, L., Lutzko, C., Crooks, G. M., Shimada, H., Coussens, L. M., Declerck, Y. A. (2005) The contribution of bone marrow-derived cells to the tumor vasculature in neuroblastoma is matrix metalloproteinase-9 dependent. Cancer Res 65 (8): 3200–3208
Acknowledgments
The authors acknowledge all the scientists who made contributions to the areas of research reviewed here that were not cited due to space constraints. The authors acknowledge support from the National Institutes of Health and a Department of Defense Era of Hope Scholar Award to LMC.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Affara, N., Andreu, P., Coussens, L. (2009). Delineating Protease Functions During Cancer Development. In: Bugge, T., Antalis, T. (eds) Proteases and Cancer. Methods in Molecular Biology™, vol 539. Humana Press. https://doi.org/10.1007/978-1-60327-003-8_1
Download citation
DOI: https://doi.org/10.1007/978-1-60327-003-8_1
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-60327-002-1
Online ISBN: 978-1-60327-003-8
eBook Packages: Springer Protocols