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Protease, an Advance Therapeutic Target in Cancer

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Pathophysiological Aspects of Proteases

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Abstract

Proteases are known to be associated with cancer development because of their aptitude to degrade extracellular matrices, which enables invasion and metastasis. Recent studies have demonstrated that a variety of substrates are the main target of these important enzymes and favour all steps of tumour evolution. An extensive number of reports have been available which shows a positive correlation between the activity of several proteases and tumour progression suggesting the usefulness of protease inhibitors as anticancer drugs. Nowadays, the cure for metastatic diseases is still a utopia and many efforts are focused on finding new sensitive biomarkers for a precise diagnostic as well as prognostic and therapy. In this scenario, understanding of the proteases, how they are involved in early to the end point in cancer progression is needed. In this review, we will focus on the role of proteases as prognostic and therapeutic targets in various types of cancers.

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References

  1. Lopez-Otin C, Hunter T (2010) The regulatory crosstalk between kinases and proteases in cancer. Nat Rev Cancer 10:278–292

    Article  CAS  PubMed  Google Scholar 

  2. Yang Y, Hao Hong H, Yin Zhang Y, Weibo CW (2009) Molecular Imaging of proteases in cancer. Cancer Growth Metastasis 2:13–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lopez-Otin C, Matrisian LM (2007) Emerging roles of proteases in tumour suppression. Nat Rev Cancer 7:800–808

    Article  CAS  PubMed  Google Scholar 

  4. Turk B (2006) Targeting proteases: successes, failures and future prospects. Nat Rev Drug Discov 5:785–799

    Article  CAS  PubMed  Google Scholar 

  5. Zucker S, Cao J, Chen WT (2000) Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment. Oncogene 19:6642–6650

    Article  CAS  PubMed  Google Scholar 

  6. Raffetto JD, Khalil RA (2008) Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. Biochem Pharmacol 75:346–359

    Article  CAS  PubMed  Google Scholar 

  7. Coussens LM, Fingleton B, Matrisian LM (2002) Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295:2387–2392

    Article  CAS  PubMed  Google Scholar 

  8. Overall CM, López-Otín C (2002) Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer 2:657–672

    Article  CAS  PubMed  Google Scholar 

  9. Lockhart AC, Braun RD, Yu D, Ross JR, Dewhirst MW, Humphrey JS, Thompson S, Williams KM, Klitzman B, Yuan F, Grichnik JM, Proia AD, Conway DA, Hurwitz HI (2003) Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor. Clin Cancer Res 9:586–593

    CAS  PubMed  Google Scholar 

  10. Woessner JF Jr (1991) Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 5:2145–2154

    Article  CAS  PubMed  Google Scholar 

  11. Chambers AF, Matrisian LM (1997) Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst 89:1260–1270

    Article  CAS  PubMed  Google Scholar 

  12. Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174

    Article  CAS  PubMed  Google Scholar 

  13. Nakopoulou L, Tsirmpa I, Alexandrou P, Louvrou A, Ampela C, Markaki S, Davaris PS (2003) MMP-2 protein in invasive breast cancer and the impact of MMP-2/TIMP-2 phenotype on overall survival. Breast Cancer Res Treat 77:145–155

    Article  CAS  PubMed  Google Scholar 

  14. Singer CF, Kronsteiner N, Marton E, Kubista M, Cullen KJ, Hirtenlehner K, Seifert M, Kubista E (2002) MMP-2 and MMP-9 expression in breast cancer-derived human fibroblasts is differentially regulated by stromal-epithelial interactions. Breast Cancer Res Treat 72:69–77

    Article  CAS  PubMed  Google Scholar 

  15. Nanda DP, Sil H, Moulik S, Biswas J, Mandal SS, Chatterjee A (2013) Matrix metalloproteinase-9 as a potential tumor marker in breast cancer. J Environ Pathol Toxicol Oncol 32:115–129

    Article  CAS  PubMed  Google Scholar 

  16. Scorilas A, Karameris A, Arnogiannaki N, Ardavanis A, Bassilopoulos P, Trangas T, Talieri M (2001) Overexpression of matrix-metalloproteinase-9 in human breast cancer: a potential favourable indicator in node-negative patients. Br J Cancer 84:1488–1496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jiang WG, Davies G, Martin TA, Parr C, Watkins G, Mason MD, Mansel RE (2006) Expression of membrane type-1 matrix metalloproteinase, MT1-MMP in human breast cancer and its impact on invasiveness of breast cancer cells. Int J Mol Med 17:583–590

    PubMed  Google Scholar 

  18. Osman NM, Osman WM (2016) SDF-1 and MMP2 cross talk in cancer cells and tumor microenvironment in non-small cell lung cancer. Egypt J Chest Dis Tubercul 65:517–525

    Article  Google Scholar 

  19. Guo CB, Wang S, Deng C, Zhang DL, Wang FL, Jin XQ (2007) Relationship between matrix metalloproteinase 2 and lung cancer progression. Mol Diagn Ther 11:183–192

    Article  CAS  PubMed  Google Scholar 

  20. Ali-Labib R, Louka ML, Galal IH, Tarek M (2014) Evaluation of matrix metalloproteinase-2 in lung cancer. Proteomics Clin Appl 8:251–257

    Article  CAS  PubMed  Google Scholar 

  21. Schveigert D, Cicenas S, Bruzas S, Samalavicius NE, Gudleviciene Z, Didziapetriene J (2013) The value of MMP-9 for breast and non-small cell lung cancer patients’ survival. Adv Med Sci 58:73–82

    Article  CAS  PubMed  Google Scholar 

  22. Zheng S, Chang Y, Hodges KB, Sun Y, Ma X, Xue Y, Williamson SR, Lopez-Beltran A, Montironi R, Cheng L (2010) Expression of KISS1 and MMP-9 in non-small cell lung cancer and their relations to metastasis and survival. Anticancer Res 30:713–718

    PubMed  Google Scholar 

  23. Hrabec E, Strek M, Nowak D, Hrabec Z (2001) Elevated level of circulating matrix metalloproteinase-9 in patients with lung cancer. Respir Med 95:1–4

    Article  CAS  PubMed  Google Scholar 

  24. Che YL, Luo SJ, Li G, Cheng M, Gao YM, Li XM, Dai JM, He H, Wang J, Peng HJ, Zhang Y, Li WY, Wang H, Liu B, Linghu H (2015) The C3G/Rap1 pathway promotes secretion of MMP-2 and MMP-9 and is involved in serous ovarian cancer metastasis. Cancer Lett 359:241–249

    Article  CAS  PubMed  Google Scholar 

  25. Kenny HA, Lengyel E (2009) MMP-2 functions as an early response protein in ovarian cancer metastasis. Cell Cycle 8:683–688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Su Y, Gao L, Teng L, Wang Y, Cui J, Peng S, Fu S (2013) Id1 enhances human ovarian cancer endothelial progenitor cell angiogenesis via PI3 K/Akt and NF-κB/MMP-2 signaling pathways. J Transl Med 11:132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Langenskiold M, Holmdahl L, Falk P, Ivarsson ML (2005) Increased plasma mmp-2 protein expression in lymph node-positive patients with colorectal cancer. Int J Colorectal Dis 20:245–252

    Article  PubMed  Google Scholar 

  28. Dragutinovic VV, Radonjic NV, Petronijevic ND, Tatic SB, Dimitrijevic IB, Radovanovic NS, Krivokapic ZV (2011) Matrix metalloproteinase-2 (mmp-2) and -9 (mmp-9) in preoperative serum as independent prognostic markers in patients with colorectal cancer. Mol Cell Biochem 355:173–178

    Article  CAS  PubMed  Google Scholar 

  29. Kryczka J, Stasiak M, Dziki L, Mik M, Dziki A, Cierniewski C (2012) Matrix metalloproteinase-2 cleavage of the beta1 integrin ectodomain facilitates colon cancer cell motility. J Biol Chem 287:36556–36566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Decock J, Paridaens R, Ye S (2008) Genetic polymorphisms of matrix metalloproteinases in lung, breast and colorectal cancer. Clin Genet 73:197–211

    Article  CAS  PubMed  Google Scholar 

  31. Leeman MF, McKay JA, Murray GI (2002) Matrix metalloproteinase 13 activity is associated with poor prognosis in colorectal cancer. J Clin Pathol 55:758–762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Huang MY, Chang HJ, Chung FY, Yang MJ, Yang YH, Wang JY, Lin SR (2010) Mmp13 is a potential prognostic marker for colorectal cancer. Oncol Rep 24:1241–1247

    Article  CAS  PubMed  Google Scholar 

  33. Lecaille F, Kaleta J, Brömme D (2002) Human and parasitic papain-like cysteine proteases: their role in physiology and pathology and recent developments ininhibitor design. Chem Rev 102:4459–4488

    Article  CAS  PubMed  Google Scholar 

  34. Chapman HA, Riese RJ, Shi GP (1997) Emerging roles for cysteine proteases in human biology. Annu Rev Physiol 59:63–88

    Article  CAS  PubMed  Google Scholar 

  35. Turk B, Turk V, Turk D (1997) Structural and functional aspects of papain-like cysteine proteinases and their protein inhibitors. Biol Chem 378:141–150

    CAS  PubMed  Google Scholar 

  36. Turk B, Turk D, Turk V (2000) Lysosomal cysteine proteases: more than scavengers. Biochim Biophys Acta 1477:98–111

    Article  CAS  PubMed  Google Scholar 

  37. Turk V, Turk B, Turk D (2001) Lysosomal cysteine proteases: facts and opportunities. EMBO J 20:4629–4633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Aronson NN Jr, Barrett AJ (1978) The specificity of cathepsin B. Hydrolysis of glucagon at the C-terminus by a peptidyldipeptidase mechanism. Biochem J 17:759–765

    Article  Google Scholar 

  39. Koga H, Mori N, Yamada H, Nishimura Y, Tokuda K, Kato K, Imoto T (1992) Endo- and aminopeptidase activities of rat cathepsin H. Chem Pharm Bull (Tokyo) 40:965–970

    Article  CAS  Google Scholar 

  40. Klemencic I, Carmona AK, Cezari MH, Juliano MA, Juliano L, Guncar G, Turk D, Krizaj I, Turk V, Turk B (2000) Biochemical characterization of human cathepsin X revealed that the enzyme is an exopeptidase, acting as carboxymonopeptidase or carboxydipeptidase. Eur J Biochem 267:5404–5412

    Article  CAS  PubMed  Google Scholar 

  41. Joyce JA, Baruch A, Chehade K, Meyer-Morse N, Giraudo E, Tsai FY, Greenbaum DC, Hager JH, Bogyo M, Hanahan D (2004) Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 5:443–453

    Article  CAS  PubMed  Google Scholar 

  42. Gocheva V, Zeng W, Ke D, Klimstra D, Reinheckel T, Peters C, Hanahan D, Joyce JA (2006) Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev 20:543–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Obermajer N, Repnik U, Jevnikar Z, Turk B, Kreft M, Kos J (2008) Cysteine protease cathepsin X modulates immune response via activation of β2 integrins. Immunology 124:76–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Alcalay NI, Sharma M, Vassmer D, Chapman B, Paul B, Zhou J, Brantley JG, Wallace DP, Maser RL, Vanden Heuvel GB (2008) Acceleration of polycystic kidney disease progression in cpk mice carrying a deletion in the homeodomain protein Cux1. Am J Physiol Renal Physiol 295:1725–1734

    Article  CAS  Google Scholar 

  45. Schmitt M, Jänicke F, Graeff H (1992) Protease matrix degradation and tumor cell spread. Fibrinolysis 6:1–17

    Google Scholar 

  46. Sloane BF, Moin K, Lah TT (1994) Lysosomal enzymes and their endogenous inhibitors in neoplasia. In: Pretlow TG, Pretlow TP (eds) Biochemical and molecular aspects of selected cancers. Academic, New York, pp 411–466

    Chapter  Google Scholar 

  47. Joyce JA, Hanahan D (2004) Multiple roles for cysteine cathepsins in cancer. Cell Cycle 3:1516–1619

    Article  CAS  PubMed  Google Scholar 

  48. Poole AR, Tiltman KJ, Recklies AD, Stoker TAM (1978) Differences in secretion of the proteinases cathepsin B at the edges of human breast carcinomas and fibroadenomas. Nature 273:545–547

    Article  CAS  PubMed  Google Scholar 

  49. Sun T, Jiang D, Zhang L, Su Q, Mao W, Jiang C (2016) Expression profile of cathepsins indicates the potential of cathepsins B and D as prognostic factors in breast cancer patients. Oncol Lett 11:575–583

    Article  PubMed  CAS  Google Scholar 

  50. Gong F, Peng X, Luo C, Shen G, Zhao C, Zou L, Li L, Sang Y, Zhao Y, Zhao X (2013) Cathepsin B as a potential prognostic and therapeutic marker for human lung squamous cell carcinoma. Mol Cancer 12:125

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Kayser K, Richter N, Hufnagl P, Kayser G, Kos J, Werle B (2003) Expression, proliferation activity and clinical significance of cathepsin B and cathepsin L in operated lung cancer. Anticancer Res 23:2767–2772

    CAS  PubMed  Google Scholar 

  52. Nishikawa H, Ozaki Y, Nakanishi T, Blomgren K, Tada T, Arakawa A, Suzumori K (2004) The role of cathepsin B and cystatin C in the mechanisms of invasion by ovarian cancer. Gynecol Oncol 92:881–886

    Article  CAS  PubMed  Google Scholar 

  53. Kawasaki G, Kato Y, Mizuno A (2002) Cathepsin expression in oral squamous cell carcinoma: relationship with clinicopathologic factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 93:446–454

    Article  PubMed  Google Scholar 

  54. Macabeo-Ong M, Shiboski CH, Silverman S, Ginzinger DG, Dekker N, Wong DTW, Jordan RCK (2003) Quantitative analysis of cathepsin L mRNA and protein expression during oral cancer progression. Oral Oncol 39:638–647

    Article  CAS  PubMed  Google Scholar 

  55. Joyce JA, Baruch A, Chehade K, Meyer-Morse N, Giraudo E (2004) Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 5:409–410

    Article  Google Scholar 

  56. Andrade SS, Gouvea IE, Silva MC, Castro ED, de Paula CA, Okamoto D, Oliveira L, Peres GB, Ottaiano T, Facina G, Nazário AC, Campos AH, Paredes-Gamero EJ, Juliano M, da Silva ID, Oliva ML, Girão MJ (2016) Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer—molecularly distinct behavior of cathepsin K in breast cancer. BMC Cancer 16:173

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Duong LT, Wesolowski GA, Leung P, Oballa R, Pickarski M (2014) Efficacy of a cathepsin K inhibitor in a preclinical model for prevention and treatment of breast cancer bone metastasis. Mol Cancer Ther 13:2898–2909

    Article  CAS  PubMed  Google Scholar 

  58. Chen B, Platt MO (2011) Multiplex zymography captures stage-specific activity profiles of cathepsins K, L, and S in human breast, lung, and cervical cancer. J Transl Med 9:109

    Article  PubMed  PubMed Central  Google Scholar 

  59. Le Gall C, Bonnelye E, Clézardin P (2008) Cathepsin K inhibitors as treatment of bone metastasis. Curr Opin Support Palliat Care 2:218–222

    Article  PubMed  Google Scholar 

  60. Tholen M, Wolanski J, Stolze B, Chiabudini M, Gajda M, Bronsert P, Stickeler E, Rospert S, Reinheckel T (2015) Stress-resistant translation of cathepsin L mRNA in breast cancer progression. J Biol Chem 290:15758–15769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Sudhan DR, Pampo C, Rice L, Siemann DW (2016) Cathepsin L inactivation leads to multimodal inhibition of prostate cancer cell dissemination in a preclinical bone metastasis model. Int J Cancer 138:2665–2677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Goll DE, Thompson VF, Li H, Wei W, Cong J (2003) The calpain system. Physiol Rev 83:731–801

    Article  CAS  PubMed  Google Scholar 

  63. Zatz M, Starling A (2005) Calpains and disease. N Engl J Med 352:2413–2423

    Article  CAS  PubMed  Google Scholar 

  64. Fougerousse F, Anderson LV, Delezoide AL, Suel L, Durand M, Beckmann JS (2000) Calpain3 expression during human cardiogenesis. Neuromuscul Disord 10:251–256

    Article  CAS  PubMed  Google Scholar 

  65. Letavernier E, Zafrani L, Perez J, Letavernier B, Haymann JP, Baud L (2012) The role of calpains in myocardial remodelling and heart failure. Cardiovasc Res 96:38–45

    Article  CAS  PubMed  Google Scholar 

  66. Leloup L, Wells A (2011) Calpains as potential anti-cancer targets. Expert Opin Ther Targets 15:309–323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Carragher NO, Frame MC (2002) Calpain: a role in cell transformation and migration. Int J Biochem Cell Biol 34:1539–1543

    Article  CAS  PubMed  Google Scholar 

  68. Carragher NO, Fonseca BD, Frame MC (2004) Calpain activity is generally elevated during transformation but has oncogene-specific biological functions. Neoplasia 6:53–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Niapour M, Yu Y, Berger SA (2008) Regulation of calpain activity by c-Myc through calpastatin and promotion of transformation in c-Myc-negative cells by calpastatin suppression. J Biol Chem 283:21371–21381

    Article  CAS  PubMed  Google Scholar 

  70. Hoskin V, Szeto A, Ghaffari A, Greer PA, Côté GP, Elliott BE (2015) Ezrin regulates focal adhesion and invadopodia dynamics by altering calpain activity to promote breast cancer cell invasion. Mol Biol Cell 26:3464–3479

    Article  PubMed  PubMed Central  Google Scholar 

  71. Storr SJ, Lee KW, Woolston CM, Safuan S, Green AR, Macmillan RD, Benhasouna A, Parr T, Ellis IO, Martin SG (2012) Calpain system protein expression in basal-like and triple-negative invasive breast cancer. Ann Oncol 23:2289–2296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Lau JK, Brown KC, Dom AM, Witte TR, Thornhill BA, Crabtree CM, Perry HE, Brown JM, Ball JG, Creel RG, Damron CL, Rollyson WD, Stevenson CD, Hardman WE, Valentovic MA, Carpenter AB, Dasgupta P (2014) Capsaicin induces apoptosis in human small cell lung cancer via the TRPV6 receptor and the calpain pathway. Apoptosis 19:1190–1201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Roumes H, Pires-Alves A, Gonthier-Maurin L, Dargelos E, Cottin P (2010) Investigation of peroxiredoxin IV as a calpain-regulated pathway in cancer. Anticancer Res 30:5085–5089

    CAS  PubMed  Google Scholar 

  74. Xu L, Deng X (2004) Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induces phosphorylation of mu- and m-calpain in association with increased secretion, cell migration, and invasion. J Biol Chem 279:53683–53690

    Article  CAS  PubMed  Google Scholar 

  75. Xu L, Deng X (2006) Protein kinase Ciota promotes nicotine-induced migration and invasion of cancer cells via phosphorylation of micro- and m-calpains. J Biol Chem 281:4457–4466

    Article  CAS  PubMed  Google Scholar 

  76. Meng XN, Jin Y, Yu Y, Bai J, Liu GY, Zhu J, Zhao YZ, Wang Z, Chen F, Lee KY, Fu SB (2009) Characterisation of fibronectin-mediated FAK signalling pathways in lung cancer cell migration and invasion. Br J Cancer 101:327–334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Storr SJ, Safuan S, Woolston CM, Abdel-Fatah T, Deen S, Chan SY, Martin SG (2012) Calpain-2 expression is associated with response to platinum based chemotherapy, progression-free and overall survival in ovarian cancer. J Cell Mol Med 16:2422–2428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Mamoune A, Luo JH, Lauffenburger DA, Wells A (2003) Calpain-2 as a target for limiting prostate cancer invasion. Cancer Res 63:4632–4640

    CAS  PubMed  Google Scholar 

  79. Libertini SJ, Tepper CG, Rodriguez V, Asmuth DM, Kung HJ, Mudryj M (2007) Evidence for calpain-mediated androgen receptor cleavage as a mechanism for androgen independence. Cancer Res 67:9001–9005

    Article  CAS  PubMed  Google Scholar 

  80. Liu T, Mendes DE, Berkman CE (2014) Prolonged androgen deprivation leads to overexpression of calpain 2: implications for prostate cancer progression. Int J Oncol 44:467–472

    Article  CAS  PubMed  Google Scholar 

  81. Lal S, La Du J, Tanguay RL, Greenwood JA (2012) Calpain 2 is required for the invasion of glioblastoma cells in the zebrafish brain microenvironment. J Neurosci Res 90:769–781

    Article  CAS  PubMed  Google Scholar 

  82. Bodnar RJ, Yates CC, Wells A (2006) IP-10 blocks vascular endothelial growth factor-induced endothelial cell motility and tube formation via inhibition of calpain. Circ Res 98:617–625

    Article  CAS  PubMed  Google Scholar 

  83. Su Y, Cui Z, Li Z, Block ER (2006) Calpain-2 regulation of VEGF-mediated angiogenesis. FASEB J 20:1443–1451

    Article  CAS  PubMed  Google Scholar 

  84. Hedstrom L (2002) Serine protease mechanism and specificity. Chem Rev 102:4501–4524

    Article  CAS  PubMed  Google Scholar 

  85. Blow DM, Birktoft JJ, Hartley BS (1969) Role of a buried acid group in the mechanism of action of chymotrypsin. Nature 221:337–340

    Article  CAS  PubMed  Google Scholar 

  86. Neurath H, Dixon GH (1957) Structure and activation of trypsinogen and chymotrypsinogen. Fed Proc 16:791–801

    CAS  PubMed  Google Scholar 

  87. Renatus M, Engh RA, Stubbs MT, Huber R, Fischer S, Kohnert U, Bode W (1997) Lysine 156 promotes the anomalous pro-enzyme activity of tPA: X-ray crystal structure of single-chain human tPA. EMBO J 16:4797–4805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Rittenhouse HG, Finlay JA, Mikolajczyk SD, Partin AW (1998) Human Kallikrein 2 (hK2) and prostate-specific antigen (PSA): two closely related, but distinct, kallikreins in the prostate. Crit Rev Clin Lab Sci 35:275–368

    Article  CAS  PubMed  Google Scholar 

  89. Black MH, Diamandis EP (2000) The diagnostic and prognostic utility of prostate specific antigen for diseases of the breast. Breast Cancer Res Treat 59:1–14

    Article  CAS  PubMed  Google Scholar 

  90. Yu H, Giai M, Diamandis EP, Katsaros D, Sutherland DJ, Levesque MA, Roagna R, Ponzone R, Sismondi P (1995) Prostate-specific antigen is a new favorable prognostic indicator for women with breast cancer. Cancer Res 55:2104–2110

    CAS  PubMed  Google Scholar 

  91. Black MH, Giai M, Ponzone R, Sismondi P, Yu H, Diamandis EP (2000) Serum total and free prostate-specific antigen for breast cancer diagnosis in women. Clin Cancer Res 6:467–473

    CAS  PubMed  Google Scholar 

  92. Lisle JE, Mertens-Walker I, Stephens CR, Stansfield SH, Clements JA, Herington AC, Stephenson SA (2015) Murine, but not human, ephrin-B2 can be efficiently cleaved by the serine protease kallikrein-4: implications for xenograft models of human prostate cancer. Exp Cell Res 333:136–146

    Article  CAS  PubMed  Google Scholar 

  93. Wolf WC, Evans DM, Chao L, Chao JA (2001) synthetic tissue kallikrein inhibitor suppresses cancer cell invasiveness. Am J Pathol 159:1797–1805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Webber MM, Waghray A, Bello D (1995) Prostate-specific antigen, a serine protease, facilitates human prostate cancer cell invasion. Clin Cancer Res 1:1089–1094

    CAS  PubMed  Google Scholar 

  95. Ishii K, Otsuka T, Iguchi K, Usui S, Yamamoto H, Sugimura Y, Yoshikawa K, Hayward SW, Hirano K (2004) Evidence that the prostate-specific antigen (PSA)/Zn2+ axis may play a role in human prostate cancer cell invasion. Cancer Lett 207:79–87

    Article  CAS  PubMed  Google Scholar 

  96. Romanov VI, Whyard T, Adler HL, Waltzer WC, Zucker S (2004) Prostate cancer cell adhesion to bone marrow endothelium: the role of prostate-specific antigen. Cancer Res 64:2083–2089

    Article  CAS  PubMed  Google Scholar 

  97. Cloutier SM, Chagas JR, Mach JP, Gygi CM, Leisinger HJ, Deperthes D (2002) Substrate specificity of human kallikrein 2 (hK2) as determined by phage display technology. Eur J Biochem 269:2747–2754

    Article  CAS  PubMed  Google Scholar 

  98. Deperthes D, Frenette G, Brillard-Bourdet M, Bourgeois L, Gauthier F, Tremblay RR, Dubé JY (1996) Potential involvement of kallikrein hK2 in the hydrolysis of the human seminal vesicle proteins after ejaculation. J Androl 17:659–665

    CAS  PubMed  Google Scholar 

  99. Lilja H (1985) A kallikrein-like serine protease in prostatic fluid cleaves the predominant seminal vesicle protein. J Clin Invest 76:1899–1903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Watt KW, Lee PJ, M’Timkulu T, Chan WP, Loor R (1986) Human prostate-specific antigen: structural and functional similarity with serine proteases. Proc Natl Acad Sci USA 83:3166–3170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Bernett MJ, Blaber SI, Scarisbrick IA, Dhanarajan P, Thompson SM, Blaber M (2002) Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system. J Biol Chem 277:24562–24570

    Article  CAS  PubMed  Google Scholar 

  102. Magklara A, Mellati AA, Wasney GA, Little SP, Sotiropoulou G, Becker GW, Diamandis EP (2003) Characterization of the enzymatic activity of human kallikrein 6: autoactivation, substrate specificity, and regulation by inhibitors. Biochem Biophys Res Commun 307:948–955

    Article  CAS  PubMed  Google Scholar 

  103. Tschesche H, Michaelis J, Kohnert U, Fedrowitz J, Oberhoff R (1989) Tissue kallikrein effectively activates latent matrix degrading metalloenzymes. Adv Exp Med Biol 247:545–548

    Article  Google Scholar 

  104. Menashi S, Fridman R, Desrivieres S, Lu H, Legrand Y, Soria C (1994) Regulation of 92-kDa gelatinase B activity in the extracellular matrix by tissue kallikrein. Ann NY Acad Sci 732:466–468

    Article  CAS  PubMed  Google Scholar 

  105. Frenette G, Tremblay RR, Lazure C, Dube JY (1997) Prostatic kallikrein hK2, but not prostate-specific antigen (hK3), activates single-chain urokinase-type plasminogen activator. Int J Cancer 71:897–899

    Article  CAS  PubMed  Google Scholar 

  106. Takayama TK, McMullen BA, Nelson PS, Matsumura M, Fujikawa K (2001) Characterization of hK4 (prostase), a prostate-specific serine protease: activation of the precursor of prostate specific antigen (pro-PSA) and single-chain urokinase-type plasminogen activator and degradation of prostatic acid phosphatase. Biochemistry 40:15341–15348

    Article  CAS  PubMed  Google Scholar 

  107. Killian CS, Corral DA, Kawinski E, Constantine RI (1993) Mitogenic response of osteoblast cells to prostatespecific antigen suggests an activation of latent TGF-β and a proteolytic modulation of cell adhesion receptors. Biochem Biophys Res Commun 192:940–947

    Article  CAS  PubMed  Google Scholar 

  108. Emanueli C, Minasi A, Zacheo A, Chao J, Chao L, Salis MB, Straino S, Tozzi MG, Smith R, Gaspa L, Bianchini G, Stillo F, Capogrossi MC, Madeddu P (2001) Local delivery of human tissue kallikrein gene accelerates spontaneous angiogenesis in mouse model of hindlimb ischemia. Circulation 103:125–132

    Article  CAS  PubMed  Google Scholar 

  109. Jin E, Fujiwara M, Pan X, Ghazizadeh M, Arai S, Ohaki Y, Kajiwara K, Takemura T, Kawanami O (2003) Protease-activated receptor (PAR)-1 and PAR-2 participate in the cell growth of alveolar capillary endothelium in primary lung adenocarcinomas. Cancer 97:703–713

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

  111. Foekens JA, Schmitt M, van Putten WL, Peters HA, Bontenbal M, Jänicke F, Klijn JG (1992) Prognostic value of urokinase-type plasminogen activator in 671 primary breast cancer patients. Cancer Res 52:6101–6105

    CAS  PubMed  Google Scholar 

  112. Janicke F, Schmitt M, Pache L, Ulm K, Harbeck N, Hofler H, Graeff H (1993) Urokinase plasminogen activator (uPA) and its inhibitor PAl- 1 are strong and independent prognostic factor in nodenegative breast cancer. Breast Cancer Res Treat 24:195–208

    Article  CAS  PubMed  Google Scholar 

  113. Duffy MJ, Reilly D, Nugent A, McDermott E, Faul C, Fennelly JJ, O’Higgins N (1992) Evaluation of proteolytic enzymes implicated in cancer metastasis as prognostic markers in breast cancer. Is J Med Sci 161:49

    Google Scholar 

  114. Duffy MJ, Reilly D, McDermott E, O’Higgins N, Fennelly JJ, Andreasen PA (1994) Urokinase plasminogen activator as a prognostic marker in different subgroups of patients with breast cancer. Cancer 74:2276–2280

    Article  CAS  PubMed  Google Scholar 

  115. Nekarda H, Siewert J, Schmitt M, Ulm K (1994) Tumor-associated proteolytic factors uPA and PAl-I and survival in totally resected gastric cancer. Lancet 343:l17

    Article  Google Scholar 

  116. Hasui Y, Marutsuka K, Suzumiya J, Kitada S, Osada Y, Sumiyoshi A (1992) The content of urokinase-type plasminogen activator antigen as a prognostic factor in urinary bladder cancer. Int J Cancer 50:871–873

    Article  CAS  PubMed  Google Scholar 

  117. Oka T, Ishida T, Nishino T, Sugimachi K (1991) Immunohistochemical evidence of urokinase plasminogen activator in primary and metastatic tumors of pulmonary carcinoma. Cancer Res 51:3522–3525

    CAS  PubMed  Google Scholar 

  118. Kobayashi H, Fujishiro S, Terao T (1994) Impact of urokinase-type plasminogen activator and its inhibitor type I on prognosis in cervical cancer of the uterus. Cancer Res 54:6539–6548

    CAS  PubMed  Google Scholar 

  119. Kuhn W, Pache L, Schmalfeldt S, Dettmar P, Schmitt M, Janicke F, Graeff H (1994) Urokinase (uPA) and PAl-I predict survival in advanced ovarian cancer patients (FIGO III) after radical surgery and platinum based chemotherapy. Gynecol Oncol 55:401–409

    Article  CAS  PubMed  Google Scholar 

  120. Barrett AJ, Cathepsin D (1970) Purification of isoenzymes from human and chicken liver. Biochem J 117:601–607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Diment S, Martin KJ, Stahl PD (1989) Cleavage of parathyroid hormone in macrophage endosomes illustrates a novel pathway for intracellular processing of proteins. J Biol Chem 264:13403–13406

    CAS  PubMed  Google Scholar 

  122. Liaudet E, Garcia M, Rochefort H (1994) Cathepsin D maturation and its stimulatory effect on metastasis are prevented by addition of KDEL retention signal. Oncogene 9:1145–1154

    CAS  PubMed  Google Scholar 

  123. Liaudet-Coopman E, Mélanie B, Danielle D, Marcel G, Glondu-Lassis M, Laurent-Matha V, Christine P, Henri R, Françoise V (2006) Cathepsin D: newly discovered functions of a long-standing aspartic protease in cancer and apoptosis. Cancer Lett 237:167–179

    Article  CAS  PubMed  Google Scholar 

  124. Vashishta A, Ohri SS, Proctor M, Fusek M, Vetvicka V (2007) Ribozyme- targeting procathepsin D and its effect on invasion and growth of breast cancer cells: an implication in breast cancer therapy. Int J Oncol 30:1223–1230

    CAS  PubMed  Google Scholar 

  125. Hu L, Roth JM, Brooks P, Luty J, Karpatkin S (2008) Thrombin up-regulates cathepsin D which enhances angiogenesis, growth, and metastasis. Cancer Res 68:4666–4673

    Article  CAS  PubMed  Google Scholar 

  126. Ohri SS, Vashishta A, Proctor M, Fusek M, Vetvicka V (2008) The propeptide of cathepsin D increases proliferation, invasion and metastasis of breast cancer cells. Int J Oncol 32:491–498

    CAS  PubMed  Google Scholar 

  127. Berchem GJ, Glondu M, Gleizes M, Brouillet JP, Garcia M, Liaudet CE (2002) Cathepsin-D affects multiple steps of tumor progression: proliferation, angiogenesis and apoptosis. Oncogene 51:5951–5955

    Article  CAS  Google Scholar 

  128. Nicotra G, Castino R, Follo C, Peracchio C, Valente G (2010) The dilemma: does tissue expression of cathepsin D reflect tumor malignancy? The question: does the assay truly mirror cathepsin D mis-function in the tumor. Cancer Biomark 7:47–64

    Article  CAS  PubMed  Google Scholar 

  129. Radisky ES, Radisky DC (2010) Matrix metalloproteinase-induced epithelial-mesenchymal transition in breast cancer. J Mammary Gland Biol Neoplasia 15:201–212

    Article  PubMed  PubMed Central  Google Scholar 

  130. Westley BR, May FE (1999) Prognostic value of cathepsin D in breast cancer. Br J Cancer 79:189–190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Rodriguez J, Vazquez J, Corte MD, Lamelas M, Bongera M (2005) Clinical significance of cathepsin D concentration in tumor cytosol of primary breast cancer. Int J Biol Markers 20:103–111

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biological Regulation, Weizmann Institute of Science, Rehovot, 76100, Israel

    Animesh Chowdhury, Donatella Romaniello & Soma Ghosh

  2. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Tapati Chakraborti & Sajal Chakraborti

  3. Department of Physiology & Cell Biology, Faculty of Health Sciences, Goldman Medical School, Ben Gurion University of the Negev, Beer Sheva, Israel

    Soumitra Roy

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  1. Animesh Chowdhury
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  2. Donatella Romaniello
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  3. Soma Ghosh
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  4. Tapati Chakraborti
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  5. Soumitra Roy
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  6. Sajal Chakraborti
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Correspondence to Animesh Chowdhury .

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  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Institute of Cardiovascular Sciences, University of Manitoba, Manitoba, Canada

    Naranjan S. Dhalla

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Chowdhury, A., Romaniello, D., Ghosh, S., Chakraborti, T., Roy, S., Chakraborti, S. (2017). Protease, an Advance Therapeutic Target in Cancer. In: Chakraborti, S., Dhalla, N. (eds) Pathophysiological Aspects of Proteases. Springer, Singapore. https://doi.org/10.1007/978-981-10-6141-7_13

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