Proteases in cutaneous malignant melanoma: Relevance as biomarker and therapeutic target

Cellular and Molecular Life Sciences

Volumn 67, Issue 23, 2010, Pages 3947-3960

  Fröhlich, Eleonore ^a  

^a MEDICAL UNIVERSITY OF GRAZ   (Austria)

Author keywords

Cathepsins; Melanoma; Metalloproteinases; Proteases; Serine proteases

Indexed keywords

ANTINEOPLASTIC AGENT; BIOLOGICAL MARKER; CATHEPSIN; CYSTATIN C; GELATINASE A; GELATINASE B; LAPATINIB; MARIMASTAT; MATRILYSIN; MATRIX METALLOPROTEINASE; MATRIX METALLOPROTEINASE 21; MATRIX METALLOPROTEINASE INHIBITOR; NEUTROPHIL COLLAGENASE; PLASMINOGEN ACTIVATOR INHIBITOR 1; PRINOMASTAT; PROTEINASE; PRX 302; SERINE PROTEINASE; TISSUE INHIBITOR OF METALLOPROTEINASE 2; TRASTUZUMAB; TX 1877; UNCLASSIFIED DRUG; UROKINASE RECEPTOR;

CANCER GROWTH; CANCER INVASION; CANCER STEM CELL; CANCER SURVIVAL; CELL TRANSFORMATION; DIFFERENTIAL DIAGNOSIS; DISEASE MARKER; DRUG TARGETING; ENZYME ACTIVATION; ENZYME ACTIVITY; GENE MUTATION; HUMAN; IMMUNOREACTIVITY; MELANOCYTE; MELANOMA; METASTASIS; NONHUMAN; PATHOGENESIS; PHENOTYPE; PREVALENCE; PROGNOSIS; PROTEIN ANALYSIS; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SURVIVAL RATE; TUMOR GROWTH;

ANIMALS; DIAGNOSIS, DIFFERENTIAL; DISEASE PROGRESSION; HUMANS; MELANOMA; PEPTIDE HYDROLASES; PROGNOSIS; SKIN NEOPLASMS; TUMOR MARKERS, BIOLOGICAL;

EID: 78651291105     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-010-0469-5     Document Type: Review

References (148)

1. Diepgen TL, Mahler V (2002) The epidemiology of skin cancer. Br J Dermatol 146(Suppl 61):1-6
2. Lens MB, Dawes M (2004) Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma. Br J Dermatol 150:179-185
3. Buzaid AC, Anderson CM (2000) The changing prognosis of melanoma. Curr Oncol Rep 2:322-328
4. MacKie RM (2000) Malignant melanoma: clinical variants and prognostic indicators. Clin Exp Dermatol 25:471-475
5. Breslow A (1970) Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 172:902-908
6. MacKie RM, Bray C, Vestey J, Doherty V, Evans A, Thomson D, Nicolson M (2007) Melanoma incidence and mortality in Scotland 1979-2003. Br J Cancer 96:1772-1777
7. Eggermont AM, Testori A, Marsden J, Hersey P, Quirt I, Petrella T, Gogas H, MacKie RM, Hauschild A (2009) Utility of adjuvant systemic therapy in melanoma. Ann Oncol 20 (Suppl 6): vi30-vi34
8. Kruger A, Kates RE, Edwards DR (2010) Avoiding spam in the proteolytic internet: future strategies for anti-metastatic MMP inhibition. Biochim Biophys Acta 1803:95-102
9. Cudic M, Fields GB (2009) Extracellular proteases as targets for drug development. Curr Protein Pept Sci 10:297-307
10. Ulisse S, Baldini E, Sorrenti S, D'Armiento M (2009) The urokinase plasminogen activator system: a target for anti-cancer therapy. Curr Cancer Drug Targets 9:32-71
11. Clark WH, Elder de Jr, Guerry DT, Epstein MN, Greene MH, Van Horn M (1984) A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma. Hum Pathol 15:1147-1165
12. Grichnik JM (2008) Melanoma, nevogenesis, and stem cell biology. J Invest Dermatol 128:2365-2380
13. Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH (2008) Identification of cells initiating human melanomas. Nature 451:345-349
14. Barnhill R, Piepkorn M, Busam K (2004) Pathology of melanocytic nevi and malignant melanoma. Springer, New York
15. Kerkela E, Saarialho-Kere U (2003) Matrix metalloproteinases in tumor progression: focus on basal and squamous cell skin cancer. Exp Dermatol 12:109-125
16. Aznavoorian S, Murphy AN, Stetler-Stevenson WG, Liotta LA (1993) Molecular aspects of tumor cell invasion and metastasis. Cancer 71:1368-1383
17. Curran S, Murray GI (1999) Matrix metalloproteinases in tumour invasion and metastasis. J Pathol 189:300-308
18. Eitzman DT, Krauss JC, Shen T, Cui J, Ginsburg D (1996) Lack of plasminogen activator inhibitor-1 effect in a transgenic mouse model of metastatic melanoma. Blood 87:4718-4722
19. Paget S (1889) The distribution of secondary growths in cancer of the breast. Lancet 133:571-573
20. Chekhun VF (2009) Stroma-regulator of cancer cell progression. Exp Oncol 31:126
21. Cullen SP, Brunet M, Martin SJ (2010) Granzymes in cancer and immunity. Cell Death Differ 17:616-623
22. Alla V, Kashyap A, Gregor S, Theobald M, Heid H, Galle PR, Strand D, Strand S (2008) Human leukocyte elastase counteracts matrix metalloproteinase-7 induced apoptosis resistance of tumor cells. Cancer Lett 268:331-339
23. Sengupta N, MacDonald TT (2007) The role of matrix metalloproteinases in stromal/epithelial interactions in the gut. Physiology (Bethesda) 22:401-409
24. Skrzydlewska E, Sulkowska M, Koda M, Sulkowski S (2005) Proteolytic-antiproteolytic balance and its regulation in carcinogenesis. World J Gastroenterol 11:1251-1266
25. Nagase H (1997) Activation mechanisms of matrix metalloproteinases. Biol Chem 378:151-160
26. Nagase H (1998) Cell surface activation of progelatinase A (proMMP-2) and cell migration. Cell Res 8:179-186
27. Folgueras AR, Pendas AM, Sanchez LM, Lopez-Otin C (2004) Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies. Int J Dev Biol 48:411-424
28. Black RA, White JM (1998) ADAMs: focus on the protease domain. Curr Opin Cell Biol 10:654-659
29. Iba K, Albrechtsen R, Gilpin BJ, Loechel F, Wewer UM (1999) Cysteine-rich domain of human ADAM 12 (meltrin alpha) supports tumor cell adhesion. Am J Pathol 154:1489-1501
30. van Hinsbergh VW, Engelse MA, Quax PH (2006) Pericellular proteases in angiogenesis and vasculogenesis. Arterioscler Thromb Vasc Biol 26:716-728
31. Stetler-Stevenson WG (2008) Tissue inhibitors of metalloproteinases in cell signaling: metalloproteinase-independent biological activities. Sci Signal 1: re6
32. Dano K, Romer J, Nielsen BS, Bjorn S, Pyke C, Rygaard J, Lund LR (1999) Cancer invasion and tissue remodeling-cooperation of protease systems and cell types. APMIS 107:120-127
33. Wernert N, Gilles F, Fafeur V, Bouali F, Raes MB, Pyke C, Dupressoir T, Seitz G, Vandenbunder B, Stehelin D (1994) Stromal expression of c-Ets1 transcription factor correlates with tumor invasion. Cancer Res 54:5683-5688 (Pubitemid 24346267)
34. Andarawewa KL, Motrescu ER, Chenard MP, Gansmuller A, Stoll I, Tomasetto C, Rio MC (2005) Stromelysin-3 is a potent negative regulator of adipogenesis participating to cancer celladipocyte interaction/crosstalk at the tumor invasive front. Cancer Res 65:10862-10871
35. Shih J-Y, Yuan A, Chen JJ-W, Yang P-C (2006) Tumor-associated macrophage: its role in cancer invasion and metastasis. J Cancer Mol 2:101-106
36. Cruz-Munoz W, Kim I, Khokha R (2006) TIMP-3 deficiency in the host, but not in the tumor, enhances tumor growth and angiogenesis. Oncogene 25:650-655
37. Hofmann UB, Westphal JR, Van Muijen GN, Ruiter DJ (2000) Matrix metalloproteinases in human melanoma. J Invest Dermatol 115:337-344
38. Nikkola J, Vihinen P, Vlaykova T, Hahka-Kemppinen M, Kahari VM, Pyrhonen S (2002) High expression levels of collagenase-1 and stromelysin-1 correlate with shorter disease-free survival in human metastatic melanoma. Int J Cancer 97:432-438
39. Hofmann UB, Westphal JR, Zendman AJ, Becker JC, Ruiter DJ, van Muijen GN (2000) Expression and activation of matrix metalloproteinase-2 (MMP-2) and its co-localization with membrane-type 1 matrix metalloproteinase (MT1-MMP) correlate with melanoma progression. J Pathol 191:245-256
40. Vaisanen A, Tuominen H, Kallioinen M, Turpeenniemi-Hujanen T (1996) Matrix metalloproteinase-2 (72 kD type IV collagenase) expression occurs in the early stage of human melanocytic tumour progression and may have prognostic value. J Pathol 180:283-289
41. Vaisanen A, Kallioinen M, Taskinen PJ, Turpeenniemi-Hujanen T (1998) Prognostic value of MMP-2 immunoreactive protein (72 kD type IV collagenase) in primary skin melanoma. J Pathol 186:51-58
42. Ray JM, Stetler-Stevenson WG (1995) Gelatinase A activity directly modulates melanoma cell adhesion and spreading. EMBO J 14:908-917
43. Hofmann UB, Eggert AA, Blass K, Brocker EB, Becker JC (2003) Expression of matrix metalloproteinases in the microenvironment of spontaneous and experimental melanoma metastases reflects the requirements for tumor formation. Cancer Res 63:8221-8225
44. Corte MD, Gonzalez LO, Corte MG, Quintela I, Pidal I, Bongera M, Vizoso F (2005) Collagenase-3 (MMP-13) expression in cutaneous malignant melanoma. Int J Biol Markers 20:242-248
45. Zigrino P, Kuhn I, Bauerle T, Zamek J, Fox JW, Neumann S, Licht A, Schorpp-Kistner M, Angel P, Mauch C (2009) Stromal expression of MMP-13 is required for melanoma invasion and metastasis. J Invest Dermatol 129:2686-2693
46. Kuivanen T, Ahokas K, Virolainen S, Jahkola T, Holtta E, Saksela O, Saarialho-Kere U (2005) MMP-21 is upregulated at early stages of melanoma progression but disappears with more aggressive phenotype. Virchows Arch 447:954-960
47. Zhao YG, Xiao AZ, Ni J, Man YG, Sang QX (2009) Expression of matrix metalloproteinase-26 in multiple human cancer tissues and smooth muscle cells. Chin J Cancer 28:1168-1175
48. Kanitakis J, Narvaez D, Claudy A (2002) Differential expression of the CD10 antigen (neutral endopeptidase) in primary versus metastatic malignant melanomas of the skin. Melanoma Res 12:241-244
49. Zigrino P, Mauch C, Fox JW, Nischt R (2005) Adam-9 expression and regulation in human skin melanoma and melanoma cell lines. Int J Cancer 116:853-859
50. Gutierrez-Fernandez A, Fueyo A, Folgueras AR, Garabaya C, Pennington CJ, Pilgrim S, Edwards DR, Holliday DL, Jones JL, Span PN, Sweep FC, Puente XS, Lopez-Otin C (2008) Matrix metalloproteinase-8 functions as a metastasis suppressor through modulation of tumor cell adhesion and invasion. Cancer Res 68:2755-2763
51. van den Oord JJ, Paemen L, Opdenakker G, de Wolf-Peeters C (1997) Expression of gelatinase B and the extracellular matrix metalloproteinase inducer EMMPRIN in benign and malignant pigment cell lesions of the skin. Am J Pathol 151:665-670
52. Cotignola J, Reva B, Mitra N, Ishill N, Chuai S, Patel A, Shah S, Vanderbeek G, Coit D, Busam K, Halpern A, Houghton A, Sander C, Berwick M, Orlow I (2007) Matrix metalloproteinase-9 (MMP-9) polymorphisms in patients with cutaneous malignant melanoma. BMC Med Genet 8:10
53. Leyon PV, Lini CC, Kuttan G (2005) Inhibitory effect of Boerhaavia diffusa on experimental metastasis by B16F10 melanoma in C57BL/6 mice. Life Sci 76:1339-1349
54. MacDougall JR, Bani MR, Lin Y, Rak J, Kerbel RS (1995) The 92-kDa gelatinase B is expressed by advanced stage melanoma cells: suppression by somatic cell hybridization with early stage melanoma cells. Cancer Res 55:4174-4181
55. Marconi C, Bianchini F, Mannini A, Mugnai G, Ruggieri S, Calorini L (2008) Tumoral and macrophage uPAR and MMP-9 contribute to the invasiveness of B16 murine melanoma cells. Clin Exp Metastasis 25:225-231
56. Houghton AM, Grisolano JL, Baumann ML, Kobayashi DK, Hautamaki RD, Nehring LC, Cornelius LA, Shapiro SD (2006) Macrophage elastase (matrix metalloproteinase-12) suppresses growth of lung metastases. Cancer Res 66:6149-6155
57. Airola K, Karonen T, Vaalamo M, Lehti K, Lohi J, Kariniemi AL, Keski-Oja J, Saarialho-Kere UK (1999) Expression of collagenases-1 and -3 and their inhibitors TIMP-1 and -3 correlates with the level of invasion in malignant melanomas. Br J Cancer 80:733-743
58. Nemeth JA, Rafe A, Steiner M, Goolsby CL (1996) TIMP-2 growth-stimulatory activity: a concentration- and cell type-specific response in the presence of insulin. Exp Cell Res 224:110-115
59. Kawasaki K, Kawakami T, Watabe H, Itoh F, Mizoguchi M, Soma y (2007) Expression of matrilysin (matrix metalloproteinase-7) in primary cutaneous and metastatic melanoma. Br J Dermatol 156:613-619
60. Vihinen P, Koskivuo I, Syrjanen K, Tervahartiala T, Sorsa T, Pyrhonen S (2008) Serum matrix metalloproteinase-8 is associated with ulceration and vascular invasion of malignant melanoma. Melanoma Res 18:268-273
61. Palavalli LH, Prickett TD, Wunderlich JR, Wei X, Burrell AS, Porter-Gill P, Davis S, Wang C, Cronin JC, Agrawal NS, Lin JC, Westbroek W, Hoogstraten-Miller S, Molinolo AA, Fetsch P, Filie AC, O'Connell MP, Banister CE, Howard JD, Buckhaults P, Weeraratna AT, Brody LC, Rosenberg SA, Samuels y (2009) Analysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma. Nat Genet 41:518-520
62. Tas F, Duranyildiz D, Oguz H, Disci R, Kurul S, Yasasever V, Topuz e (2005) Serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 in patients with malignant melanoma. Med Oncol 22:39-44
63. Gould Rothberg BE, Bracken MB, Rimm DL (2009) Tissue biomarkers for prognosis in cutaneous melanoma: a systematic review and meta-analysis. J Natl Cancer Inst 101:452-474
64. Bosserhoff AK (2006) Novel biomarkers in malignant melanoma. Clin Chim Acta 367:28-35
65. Oku T, Ata N, Yonezawa K, Tokai H, Fujii H, Shinagawa A, Ohuchi E, Saiki I (1997) Antimetastatic and antitumor effect of a recombinant human tissue inhibitor of metalloproteinases-2 in murine melanoma models. Biol Pharm Bull 20:843-849
66. Shalinsky DR, Brekken J, Zou H, McDermott CD, Forsyth P, Edwards D, Margosiak S, Bender S, Truitt G, Wood A, Varki NM, Appelt K (1999) Broad antitumor and antiangiogenic activities of AG3340, a potent and selective MMP inhibitor undergoing advanced oncology clinical trials. Ann NY Acad Sci 878:236-270
67. Quirt I, Bodurth A, Lohmann R, Rusthoven J, Belanger K, Young V, Wainman N, Stewar W, Eisenhauer e (2002) Phase II study of marimastat (BB-2516) in malignant melanoma: a clinical and tumor biopsy study of the National Cancer Institute of Canada Clinical Trials Group. Invest New Drugs 20:431-437 (Pubitemid 35252787)
68. Dass K, Ahmad A, Azmi AS, Sarkar SH, Sarkar FH (2008) Evolving role of uPA/uPAR system in human cancers. Cancer Treat Rev 34:122-136
69. Danø K, Andreasen PA, Grøndahl-Hansen J, Kristensen P, Nielsen LS, Skriver L (1985) Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res 44:139-266
70. Schmitt M, Jánicke F, Moniwa N, Chucholowski N, Pache L, Graeff H (1992) Tumor-associated urokinase-type plasminogen activator: biological and clinical significance. Biol Chem Hoppe Seyler 373:611-622
71. Ossowski L, Aguirre-Ghiso JA (2000) Urokinase receptor and integrin partnership: coordination of signaling for cell adhesion, migration and growth. Curr Opin Cell Biol 12:613-620
72. Loskutoff DJ, Curriden SA, Hu G, Deng G (1999) Regulation of cell adhesion by PAI-1. APMIS 107:54-61
73. Noel A, Maillard C, Rocks N, Jost M, Chabottaux V, Sounni NE, Maquoi E, Cataldo D, Foidart JM (2004) Membrane associated proteases and their inhibitors in tumour angiogenesis. J Clin Pathol 57:577-584
74. Bajou K, Noel A, Gerard RD, MassonV, BrunnerN, Holst Hansen C, Skobe M, Fusenig NE, Carmeliet P, Collen D, Foidart JM (1998) Absence of host plasminogen activator inhibitor1 prevents cancer invasion and vascularization. Nat Med 4:923-928
75. Khin EE, Kikkawa F, Ino K, Kajiyama H, Suzuki T, Shibata K, Tamakoshi K, Nagasaka T, Mizutani S (2003) Dipeptidyl peptidase IV expression in endometrial endometrioid adenocarcinoma and its inverse correlation with tumor grade. Am J Obstet Gynecol 188:670-676 (Pubitemid 36332432)
76. Kajiyama H, Kikkawa F, Suzuki T, Shibata K, Ino K, Mizutani S (2002) Prolonged survival and decreased invasive activity attributable to dipeptidyl peptidase IV overexpression in ovarian carcinoma. Cancer Res 62:2753-2757
77. Tanaka T, Umeki K, Yamamoto I, Sakamoto F, Noguchi S, Ohtaki S (1995) CD26 (dipeptidyl peptidase IV/DPP IV) as a novel molecular marker for differentiated thyroid carcinoma. Int J Cancer 64:326-331
78. Wilson MJ, Ruhland AR, Quast BJ, Reddy PK, Ewing SL, Sinha AA (2000) Dipeptidylpeptidase IV activities are elevated in prostate cancers and adjacent benign hyperplastic glands. J Androl 21:220-226
79. Stabuc B, Markovic J, Bartenjev I, Vrhovec I, Medved U, Kocijancic B (2003) Urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 and type 2 in stage I malignant melanoma. Oncol Rep 10:635-639
80. Hearing VJ, Law LW, Corti A, Appella E, Blasi F (1988) Modulation of metastatic potential by surface urokinase of murine melanoma cells. Cancer Res 48:1270-1278
81. Sordat B, Reiter L, Cajot JF (1990) Modulation of the malignant phenotype with the urokinase-type plasminogen activator and the type I plasminogen activator inhibitor. Cell Differ Dev 32:277-285
82. Min HY, Doyle LV, Vitt CR, Zandonella CL, Stratton-Thomas JR, Shuman MA, Rosenberg S (1996) Urokinase receptor antagonists inhibit angiogenesis and primary tumor growth in syngeneic mice. Cancer Res 56:2428-2433 (Pubitemid 26154094)
83. Delbaldo C, Masouye I, Saurat JH, Vassalli JD, Sappino AP (1994) Plasminogen activation in melanocytic neoplasia. Cancer Res 54:4547-4552
84. Brooks TD, Slomp J, Quax PH, De Bart AC, Spencer MT, Verheijen JH, Charlton PA (2000) Antibodies to PAI-1 alter the invasive and migratory properties of human tumour cells in vitro. Clin Exp Metastasis 18:445-453
85. Mueller BM (1996) Different roles for plasminogen activators and metalloproteinases in melanoma metastasis. Curr Top Microbiol Immunol 213:65-80
86. Gershtein ES, Medvedeva SV, Babkina IV, Kushlinskii NE, Trapeznikov NN (2001) Tissue- and urokinase-type plasminogen activators and type 1 plasminogen activator inhibitor in melanomas and benign skin pigment neoplasms. Bull Exp Biol Med 132:670-674
87. de Vries TJ, Quax PH, Denijn M, Verrijp KN, Verheijen JH, Verspaget HW, Weidle UH, Ruiter DJ, van Muijen GN (1994) Plasminogen activators, their inhibitors, and urokinase receptor emerge in late stages of melanocytic tumor progression. Am J Pathol 144:70-81
88. Fröhlich E, Maier E, Mack AF, Garbe C (2009) Dipeptidyl peptidase II is not a marker for progression in melanoma. J Dermatol Sci 53:68-71
89. Pethiyagoda CL, Welch DR, Fleming TP (2000) Dipeptidyl peptidase IV (DPPIV) inhibits cellular invasion of melanoma cells. Clin Exp Metastasis 18:391-400
90. Van den Oord JJ (1998) Expression of CD26/dipeptidyl-peptidase IV in benign and malignant pigment-cell lesions of the skin. Br J Dermatol 138:615-621
91. Fröhlich E, Kröber S (2008) Activity and expression of dipeptidyl peptidase IV and cathepsin H in human cutaneous melanoma compared to other common cancers. In: Scháfer L, Richter e (eds) New Research Communications on tumor markers. Nova, New York, pp 81-90
92. Denk AE, Bettstetter M, Wild PJ, Hoek K, Bataille F, Dietmaier W, Bosserhoff AK (2007) Loss of maspin expression contributes to a more invasive potential in malignant melanoma. Pigment Cell Res 20:112-119
93. Vereecken P, Reynaert S, Lalmand MC, Zouaoui-Boudjeltia K, Heenen M, Van den Heule B, Petein M (2006) Decreased immunoreactive maspin expression in intermediate thickness and thick primary melanoma lesions. J Int Med Res 34:52-57
94. Chua R, Setzer S, Govindarajan B, Sexton D, Cohen C, Arbiser JL (2009) Maspin expression, angiogenesis, prognostic parameters, and outcome in malignant melanoma. J Am Acad Dermatol 60:758-766
95. Ferrier CM, Van Geloof WL, Straatman H, Van de Molengraft FJ, Van Muijen GN, Ruiter DJ (2002) Spitz naevi may express components of the plasminogen activation system. J Pathol 198:92-99
96. Hanekom GS, Stubbings HM, Kidson SH (2002) The active fraction of plasmatic plasminogen activator inhibitor type 1 as a possible indicator of increased risk for metastatic melanoma. Cancer Detect Prev 26:50-59
97. Czekay RP, Loskutoff DJ (2004) Unexpected role of plasminogen activator inhibitor 1 in cell adhesion and detachment. Exp Biol Med (Maywood) 229:1090-1096
98. Spiess E, Brüning A, Gack S, Ulbricht B, Spring H, Trefz G, Ebert W (1994) Cathepsin B activity in human lung tumor cell lines: ultrastructural localization, pH sensitivity, and inhibitor status at the cellular level. J Histochem Cytochem 42:917-929
99. Lorenzo K, Ton P, Clark JL, Coulibaly S, Mach L (2000) Invasive properties of murine squamous carcinoma cells: secretion of matrix-degrading cathepsins is attributable to a deficiency in the mannose 6-phosphate/insulin- like growth factor II receptor. Cancer Res 60:4070-4076
100. Sameni M, Moin K, Sloane BF (2000) Imaging proteolysis by living human breast cancer cells. Neoplasia 2:496-504
101. Garnero P, Borel O, Byrjalsen I, Ferreras M, Drake FH, McQueney MS, Foged NT, Delmas PD, Delaisse JM (1998) The collagenolytic activity of cathepsin K is unique among mammalian proteinases. J Biol Chem 273:32347-32352
102. Berchem G, Glondu M, Gleizes M, Brouillet JP, Vignon F, Garcia M, Liaudet-Coopman E (2002) Cathepsin-D affects multiple tumor progression steps in vivo: proliferation, angiogenesis and apoptosis. Oncogene 21:5951-5955
103. Wolf M, Clark-Lewis I, Buri C, Langen H, Lis M, Mazzucchelli L (2003) Cathepsin D specifically cleaves the chemokines macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, and SLC that are expressed in human breast cancer. Am J Pathol 162:1183-1190
104. Reddy VY, Zhang QY, Weiss SJ (1995) Pericellular mobilization of the tissue-destructive cysteine proteinases, cathepsins B, L, and S, by human monocyte-derived macrophages. Proc Natl Acad Sci USA 92:3849-3853
105. Kirschke H (1997) Lysosomal cysteine peptidases and malignant tumours. In: Ansorge S, Langner J (eds) Cellular peptidases in immune functions and diseases. Plenum, New York, pp 253-257
106. Sloane BF, Dunn JR, Honn KV (1981) Lysosomal cathepsin B: correlation with metastatic potential. Science 212:1151-1153
107. Rozhin J, Wade RL, Honn KV, Sloane BF (1989) Membraneassociated cathepsin L: a role in metastasis of melanomas. Biochim Biophys Res Comm 164:556-561
108. Stabuc B, Mrevlje Z, Markovic J, Stabuc-Silih M (2006) Expression and prognostic significance of cathepsin L in early cutaneous malignant melanoma. Neoplasma 53:259-262
109. Yang Z, Cox JL (2007) Cathepsin L increases invasion and migration of B16 melanoma. Cancer Cell Int 7:8
110. Fröhlich E, Schaumburg-Lever G, Klessen C (1995) Immunocytochemical and immunelectron microscopic demonstration of cathepsin B in human malignant melanoma. Br J Dermatol 132:867-875
111. Gong Q, Chan SJ, Bajkowsky AS, Steiner DF, Frankfater A (1993) Characterization of the cathepsin B gene and multiple mRNAs in human tissues: evidence for alternative splicing of cathepsin B pre-mRNA. DNA Cell Biol 12:299-309
112. Tsushima H, Hyodoh F, Yoshida E, Ueki A, Hopsu-Havu VK (1992) Inactive cathepsin B-like enzyme in human melanoma culture medium. Melanoma Res 1:341-347
113. Fröhlich E, Schlagenhauff B, Möhrle M, Weber E, Klessen C, Rassner G (2001) Activity, expression and transcription rate of the cathepsins B, D, H and L in cutaneous malignant melanoma. Cancer 91:972-982
114. Moin K, Cao L, Day NA, Koblinski JE, Sloane BF (1998) Tumor cell membrane cathepsin B. Biol Chem 379:1093-1099
115. Sloane BF, Rozhin J, Johnson K, Taylor H, Crissman JD, Honn KV (1986) Cathepsin B: association with plasma membrane in metastatic tumors. Proc Natl Acad Sci USA 83:2483-2487
116. Fröhlich E, Möhrle M, Klessen C (2004) Cathepsins in basal cell carcinomas: activity, immunoreactivity and mRNA staining of the cathepsins B, D, H, and L. Arch Dermatol Res 295:411-421
117. Jedeszko C, Sloane BF (2004) Cysteine cathepsins in human cancer. Biol Chem 385:1017-1027
118. Sever N, Filipic M, Brzin J, Lah TT (2002) Effect of cysteine proteinase inhibitors on murine B16 melanoma cell invasion in vitro. Biol Chem 383:839-842
119. Rozhin J, Sameni M, Ziegler G, Sloane BF (1994) Pericellular pH affects distribution and secretion of cathepsin B in malignant cells. Cancer Res 54:6517-6525
120. Szpaderska AM, Frankfater A (2001) An intracellular form of cathepsin B contributes to invasiveness in cancer. Cancer Res 61:3493-3500
121. Rousselet N, Mills L, Jean D, Tellez C, Bar-Eli M, Frade R (2004) Inhibition of tumorigenicity and metastasis of human melanoma cells by anti-cathepsin L single chain variable fragment. Cancer Res 64:146-151
122. Ulmer A, Korber V, Schmid H, Fierlbeck G (1998) Increased activity of cathepsin B in fibroblasts isolated from primary melanoma in comparison to fibroblasts from normal skin. Exp Dermatol 7:14-17
123. Podhajcer OL, Bover L, Bravo AI, Ledda MF, Kairiyama C, Calb I, Guerra L, Capony F, Mordoh J (1995) Expression of cathepsin D in primary and metastatic human melanoma and dysplastic nevi. J Invest Dermatol 104:340-344
124. Goldmann T, Suter L, Ribbert D, Otto F (1999) The expression of proteolytic enzymes at the dermal invading front of primary cutaneous melanoma predicts metastasis. Pathol Res Pract 195:171-175
125. Kozlowski L, Wojtukiewicz MZ, Ostrowska H (2000) Cathepsin A activity in primary and metastatic human melanocytic tumors. Arch Dermatol Res 292:68-71
126. Quintanilla-Dieck MJ, Codriansky K, Keady M, Bhawan J, Runger TM (2008) Cathepsin K in melanoma invasion. J Invest Dermatol 128:2281-2288
127. Kawakubo T, Okamoto K, Iwata J, Shin M, Okamoto Y, Yasukochi A, Nakayama KI, Kadowaki T, Tsukuba T, Yamamoto K (2007) Cathepsin e prevents tumor growth and metastasis by catalyzing the proteolytic release of soluble TRAIL from tumor cell surface. Cancer Res 67:10869-10878
128. Tsushima H, Sumi H, Hamanaka K, Toki N, Sato H, Mihara H (1985) Cysteine protease inhibitors isolated from human malignant melanoma tissue. J Lab Clin Med 106:712-717
129. Boike G, Lah T, Sloane BF, Rozhin J, Honn K, Guirguis R, Stracke ML, Liotta LA, Schiffmann e (1992) A possible role for cysteine proteinase and its inhibitors in motility of malignant melanoma and other tumour cells. Melanoma Res 1:333-340
130. Kos J, Stabuc B, Schweiger A, Krasovec M, Cimerman N, Kopitar Jerala N, Vrhovec I (1997) Cathepsins B, H, and L and their inhibitors stefin A and cystatin C in sera of melanoma patients. Clin Cancer Res 3:1815-1822
131. Yoshii A, Kageshita T, Tsushima H, Ono T (1995) Clinical relevance of cathepsin B-like enzyme activity and cysteine proteinase inhibitor in melanocytic tumours. Arch Dermatol Res 287:209-213
132. Schurigt U, Sevenich L, Vannier C, Gajda M, Schwinde A, Werner F, Stahl A, von Elverfeldt D, Becker AK, Bogyo M, Peters C, Reinheckel T (2008) Trial of the cysteine cathepsin inhibitor JPM-OEt on early and advanced mammary cancer stages in the MMTV-PyMT-transgenic mouse model. Biol Chem 389:1067-1074
133. Ervin H, Cox JL (2005) Late stage inhibition of hematogenous melanoma metastasis by cystatin C over-expression. Cancer Cell Int 5:14
134. Konstantinopoulos PA, Karamouzis MV, Papatsoris AG, Papavassiliou AG (2008) Matrix metalloproteinase inhibitors as anticancer agents. Int J Biochem Cell Biol 40:1156-1168
135. Murphy CG, Modi S (2009) HER2 breast cancer therapies: a review. Biologics 3:289-301
136. Williams SA, Merchant RF, Garrett-Mayer E, Isaacs JT, Buckley JT, Denmeade SR (2007) A prostate-specific antigenactivated channel-forming toxin as therapy for prostatic disease. J Natl Cancer Inst 99:376-385
137. Liu S, Wang H, Currie BM, Molinolo A, Leung HJ, Moayeri M, Basile JR, Alfano RW, Gutkind JS, Frankel AE, Bugge TH, Leppla SH (2008) Matrix metalloproteinase-activated anthrax lethal toxin demonstrates high potency in targeting tumor vasculature. J Biol Chem 283:529-540
138. Atkinson JM, Siller CS, Gill JH (2008) Tumour endoproteases: the cutting edge of cancer drug delivery? Br J Pharmacol 153:1344-1352
139. Graham CH, Forsdike J, Fitzgerald CJ, Macdonald-Goodfellow S (1999) Hypoxia-mediated stimulation of carcinoma cell invasiveness via upregulation of urokinase receptor expression. Int J Cancer 80:617-623
140. Frade R, Rousselet N, Jean D (2008) Intratumoral gene delivery of anti-cathepsin L single-chain variable fragment by lentiviral vector inhibits tumor progression induced by human melanoma cells. Cancer Gene Ther 15:591-604
141. Sun B, Zhang D, Zhang S, Zhang W, Guo H, Zhao X (2007) Hypoxia influences vasculogenic mimicry channel formation and tumor invasion-related protein expression in melanoma. Cancer Lett 249:188-197
142. Zhao W, Darmanin S, Fu Q, Chen J, Cui H, Wang J, Okada F, Hamada J, Hattori Y, Kondo T, Hamuro J, Asaka M, Kobayashi M (2005) Hypoxia suppresses the production of matrix metall oproteinases and the migration of human monocytederived dendritic cells. Eur J Immunol 35:3468-3477
143. Miyake K, Shimada M, Nishioka M, Sugimoto K, Batmunkh E, Uto Y, Nagasawa H, Hori H (2009) Downregulation of matrix metalloprotease-9 and urokinase plasminogen activator by TX-1877 results in decreased tumor growth and metastasis on xenograft model of rectal cancer. Cancer Chemother Pharmacol 64:885-892
144. Shenoy D, Little S, Langer R, Amiji M (2005) Poly (ethylene oxide)-modified poly (beta-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs: part 2. In vivo distribution and tumor localization studies. Pharm Res 22:2107-2114
145. Na K, Bum Lee T, Park KH, Shin EK, Lee YB, Choi HK (2003) Self-assembled nanoparticles of hydrophobically-modified polysaccharide bearing vitamin H as a targeted anti-cancer drug delivery system. Eur J Pharm Sci 18:165-173
146. Lee ES, Shin HJ, Na K, Bae YH (2003) Poly (L-histidine)-PEG block copolymer micelles and pH-induced destabilization. J Control Release 90:363-374
147. Huh CG, Hakansson K, Nathanson CM, Thorgeirsson UP, Jonsson N, Grubb A, Abrahamson M, Karlsson S (1999) Decreased metastatic spread in mice homozygous for a null allele of the cystatin C protease inhibitor gene. Mol Pathol 52:332-340
148. Wald M, Olejar T, Sebkova V, Zadinova M, Boubelik M, Pouckova P (2001) Mixture of trypsin, chymotrypsin and papain reduces formation of metastases and extends survival time of C57Bl6 mice with syngeneic melanoma B16. Cancer Chemother Pharmacol 47 (Suppl): S16-S22