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Clinical & Translational Metabolism
Published in: Clinical Reviews in Bone and Mineral Metabolism 2/2011

01-06-2011 | Original Paper

The Emerging Relevance of the Cysteine Protease Cathepsin S in Disease

Authors: Donna M. Small, Roberta E. Burden, Christopher J. Scott

Published in: Clinical & Translational Metabolism | Issue 2/2011

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Abstract

Cathepsin S is a lysosomal cysteine protease that has been shown to play a key role in MHC class II antigen presentation. Consequently, it has been extensively evaluated as a therapeutic target in autoimmune diseases, such as rheumatoid arthritis and psoriasis. Additionally, clinical and mechanistic evidence is emerging, revealing its inappropriate expression and secretion in a wide range of disease states including atherosclerosis and tumourigenesis. This review covers the known role and consequences of cathepsin S activity in these pathological disorders, highlighting various studies that have demonstrated its utility as a therapeutic target. This review also examines challenges that exist towards the development of agents that specifically target this protease and discusses the studies to date that have applied cathepsin S inhibitors in disease models.
Literature
1.
Turk V, Turk B, Turk D. Lysosomal cysteine proteases: facts and opportunities. EMBO J. 2001;20(17):4629–33.PubMedCrossRef
2.
Brömme D, Kaleta J. Thiol-dependent cathepsins: pathophysiological implications and recent advances in inhibitor design. Curr Pharm Des. 2002;8(18):1639–58.PubMedCrossRef
3.
Musil D, Zucic D, Turk D, Engh RA, Mayr I, Huber R, et al. The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity. EMBO J. 1991;10(9):2321–30.PubMed
4.
KlemencÏicÏ I, Carmona AK, Cezari MH, Juliano MA, Juliano L, Guncar G, et al. Biochemical characterization of human cathepsin X revealed that the enzyme is an exopeptidase, acting as carboxymonopeptidase or carboxydipeptidase. Eur J Biochem. 2000;267(17):5404–12.
5.
Vasiljeva O, Dolinar M, Turk V, Turk B. Recombinant human cathepsin H lacking the mini chain is an endopeptidase. Biochemistry. 2003;42(46):13522–8.PubMedCrossRef
6.
Brix K, Dunkhorst A, Mayer K, Jordans S. Cysteine cathepsins: cellular roadmap to different functions. Biochimie. 2008;90:194–207.PubMedCrossRef
7.
Chen WT. Membrane proteases: roles in tissue remodeling and tumour invasion. Curr Opin Cell Biol. 1992;4(5):802–9.PubMedCrossRef
8.
Cavallo-Medved D, Mai J, Dosescu J, Sameni M, Sloane BF. Caveolin-1 mediates the expression and localization of cathepsin B, pro-urokinase plasminogen activator and their cell-surface receptors in human colorectal carcinoma cells. J Cell Sci. 2005;118(Pt 7):1493–503.PubMedCrossRef
9.
Goulet B, Baruch A, Moon NS, Poirier M, Sansregret LL, Erickson A, et al. A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP/Cux transcription factor. Mol Cell. 2004;14(2):207–19.PubMedCrossRef
10.
Goulet B, Sansregret L, Leduy L, Bogyo M, Weber E, Chauhan SS, et al. Increased expression and activity of nuclear cathepsin L in cancer cells suggests a novel mechanism of cell transformation. Mol Cancer Res. 2007;5(9):899–907.PubMedCrossRef
11.
Shi GP, Villadangos JA, Dranoff G, Small C, Gu L, Haley KJ, et al. Cathepsin S required for normal MHC class II peptide loading and germinal center development. Immunity. 1999;10(2):197–206.PubMedCrossRef
12.
Wex T, Bühling F, Wex H, Günther D, Malfertheiner P, Weber E, et al. Human cathepsin W, a cysteine protease predominantly expressed in NK cells, is mainly localized in the endoplasmic reticulum. J Immunol. 2001;167(4):2172–8.PubMed
13.
Kuester D, Vieth M, Peitz U, Kahl S, Stolte M, Roessner A. Upregulation of cathepsin W-expressing T cells is specific for autoimmune atrophic gastritis compared to other types of chronic gastritis. World J Gastroenterol. 2005;11(38):5951–7.PubMed
14.
Li YP, Chen W. Characterization of mouse cathepsin K gene, the gene promoter, and the gene expression. J Bone Miner Res. 1999;14(4):487–99.PubMedCrossRef
15.
Kuester D, Lippert H, Roessner A, Krueger S. The cathepsin family and their role in colorectal cancer. Pathol Res Pract. 2008;2047:491–500.CrossRef
16.
Pham CT, Ley TJ. Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo. Proc Natl Acad Sci USA. 1999;96(15):8627–32.PubMedCrossRef
17.
Roth W, Deussing J, Botchkarev VA, Pauly-Evers M, Saftig P, Hafner A, et al. Cathepsin L deficiency as molecular defect of furless: hyperproliferation of keratinocytes and perturbation of hair follicle cycling. FASEB J. 2000;13:2075–86.CrossRef
18.
Saftig P, Hunziker E, Wehmeyer O, Jones S, Boyde A, Rommerskirch W, et al. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc Natl Acad Sci USA. 1998;95(23):13453–8.PubMedCrossRef
19.
Felbor U, Kessler B, Mothes W, Goebel HH, Ploegh HL, Bronson RT, et al. Neuronal loss and brain atrophy in mice lacking cathepsins B and L. Proc Natl Acad Sci USA. 2002;99(12):7883–8.PubMedCrossRef
20.
Kirschke H, Schmidt I, Wiederanders B. Cathepsin S. The cysteine proteinase from bovine lymphoid tissue is distinct from cathepsin L (EC 3.4.22.15). Biochem J. 1986;240(2):455–9.PubMed
21.
Kirschke H, Wiederanders B, Brömme D, Rinne A. Cathepsin S from bovine spleen. Purification, distribution, intracellular localization and action on proteins. Biochem J. 1989;264(2):467–73.PubMed
22.
Shi GP, Munger JS, Meara JP, Rich DH, Chapman HA. Molecular cloning and expression of human alveolar macrophage cathepsin S, an elastinolytic cysteine protease. J Biol Chem. 1992;267(11):7258–62.PubMed
23.
Wiederanders B, Brömme D, Kirschke H, von Figura K, Schmidt B, Peters C. Phylogenetic conservation of cysteine proteinases. Cloning and expression of a cDNA coding for human cathepsin S. J Biol Chem. 1992;267(19):13708–13.PubMed
24.
Riese RJ, Wolf PR, Brömme D, Natkin LR, Villadangos JA, Ploegh HL. Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading. Immunity. 1996;4(4):357–66.PubMedCrossRef
25.
Chapman HA, Riese RJ, Shi GP. Emerging role for cysteine proteases in human biology. Annu Rev Physiol. 1997;59:63–88.PubMedCrossRef
26.
Turk D, Podobnik M, Kuhelj R, Dolinar M, Turk V. Crystal structures of human procathepsin B at 3.2 and 3.3 Angstroms resolution reveal an interaction motif between a papain-like cysteine protease and its propeptide. FEBS Lett. 1996;384(3):211–4.PubMedCrossRef
27.
Guay J, Falgueyret JP, Ducret A, Percival MD, Mancini JA. Potency, selectivity of inhibition of cathepsin K, L and S by their respective propeptides. Eur J Biochem. 2000;267:6311–8.PubMedCrossRef
28.
Vasiljeva O, Turk B. Dual contrasting roles of cysteine cathepsins in cancer progression: apoptosis versus tumour invasion. Biochimie. 2008;90(2):380–6.PubMedCrossRef
29.
Turk B, Turk D, Turk V. Lysosomal cysteine proteases: more than scavengers. Biochim Biophys Acta. 2000;1477:98–111.PubMedCrossRef
30.
Vasiljeva O, Dolinar M, Pungercar JR, Turk V, Turk B. Recombinant human procathepsin S is capable of autocatalytic processing at neutral pH in the presence of glycosaminoglycans. FEBS Lett. 2005;579(5):1285–90.PubMedCrossRef
31.
Brömme D, Rinne R, Kirschke H. Tight-binding inhibition of cathepsin S by cystatins. Biomed Biochim Acta. 1991;50(4–6):631–5.PubMed
32.
Bode W, Huber R. Structural basis of the endoproteinase-protein inhibitor interaction. Biochim Biophys Acta. 2000;1477(1–2):241–52.PubMedCrossRef
33.
Grzonka Z, Jankowska E, Kasprzykowski F, Kasprzykowska R, Lankiewicz L, Wiczk W, et al. Structural studies of cysteine proteases and their inhibitors. Acta Biochim Pol. 2001;48(1):1–20.PubMed
34.
Shi GP, Webb AC, Foster KE, Knoll JH, Lemere CA, Munger JS, et al. Human cathepsin S: chromosomal localization, gene structure, and tissue distribution. J Biol Chem. 1994;269(15):11530–6.PubMed
35.
Storm van’s Gravesande K, Layne MD, Ye Q, Le L, Baron RM, Perrella MA, et al. IFN regulatory factor-1 regulates IFN-gamma-dependent cathepsin S expression. J Immunol. 2002;168(9):4488.PubMed
36.
Seo HR, Bae S, Lee YS. Radiation-induced cathepsin S is involved in radioresistance. Int J Cancer. 2009;124(8):1794–801.PubMedCrossRef
37.
Riese RJ, Mitchell RN, Villadangos JA, Shi GP, Palmer JT, Karp ER, et al. Cathepsin S activity regulates antigen presentation and immunity. J Clin Invest. 1998;101(11):2351–633.PubMedCrossRef
38.
Nakagawa TY, Brissette WH, Lira PD, Griffiths RJ, Petrushova N, Stock J, et al. Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice. Immunity. 1999;10:207–17.PubMedCrossRef
39.
Riese RJ, Shi GP, Villadangos J, Stetson D, Driessen C, Lennon-Dumenil AM, et al. Regulation of CD1 function and NK1.1(+) T cell selection and maturation by cathepsin S. Immunity. 2001;15(6):909–19.PubMedCrossRef
40.
Costantino CM, Ploegh HL, Hafler DA. Cathepsin S regulates class II MHC processing in human CD4+ HLA-DR+ T cells. J Immunol. 2009;183(2):945–52.PubMedCrossRef
41.
Beers C, Burich A, Kleijmeer MJ, Griffith JM, Wong P, Rudensky AY. Cathepsin S controls MHC class II-mediated antigen presentation by epithelial cells in vivo. J Immunol. 2005;174(3):1205–12.PubMed
42.
Shi GP, Bryant RA, Riese R, Verhelst S, Driessen C, Li Z, et al. Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages. J Exp Med. 2000;191(7):1177–86.PubMedCrossRef
43.
Beers C, Honey K, Fink S, Forbush K, Rudensky A. Differential regulation of cathepsin S and L in interferon gamma-treated macrophages. J Exp Med. 2003;197(2):169–79.PubMedCrossRef
44.
Fiebiger E, Meraner P, Weber E, Fang IF, Stingl G, Ploegh H, et al. Cytokines regulate proteolysis in major histocompatibility complex class II-dependent antigen presentation by dendritic cells. J Exp Med. 2001;193(8):881–92.PubMedCrossRef
45.
Faure-André G, Vargas P, Yuseff MI, Heuzé M, Diaz J, Lankar D, et al. Regulation of dendritic cell migration by CD74, the MHC class II-associated invariant chain. Science. 2008;322(5908):1705–10.PubMedCrossRef
46.
Plüger EB, Boes M, Alfonso C, Schröter CJ, Kalbacher H, Ploegh HL, et al. Specific role for cathepsin S in the generation of antigenic peptides in vivo. Eur J Immunol. 2002;32(2):467–76.PubMedCrossRef
47.
Shen L, Sigal LJ, Boes M, Rock KL. Important role of cathepsin S in generating peptides for TAP-independent MHC class I crosspresentation in vivo. Immunity. 2004;21(2):155–65.PubMedCrossRef
48.
Saegusa K, Ishimaru N, Yanagi K, Arakaki R, Ogawa K, Saito I, et al. Cathepsin S inhibitor prevents autoantigen presentation and autoimmunity. J Clin Invest. 2002;110:361–9.PubMed
49.
Kala M, Chen CR, McLachlan SM, Rapoport B, Aliesky H, Chapman HA. Cathepsin S is not crucial to TSHR processing and presentation in a murine model of Graves’ disease. Immunology. 2005;116:532–40.PubMed
50.
Yang H, Kala M, Scott BG, Goluszko E, Chapman HA, Christadoss P. Cathepsin S is required for murine autoimmune myasthenia gravis pathogenesis. J Immunol. 2005;174:1729–37.PubMed
51.
Firestein GS. Immunologic mechanisms in the pathogenesis of rheumatoid arthritis. J Clin Rheumatol. 2005;11(3 Suppl):S39–44.PubMedCrossRef
52.
Yasuda Y, Kaleta J, Brömme D. The role of cathepsins in osteoporosis and arthritis: rationale for the design of new therapeutics. Adv Drug Deliv Rev. 2005;57(7):973–93.PubMedCrossRef
53.
Pozgan U, Caglic D, Rozman B, Nagase H, Turk V, Turk B. Expression and activity profiling of selected cysteine cathepsins and matrix metalloproteinases in synovial fluids from patients with rheumatoid arthritis and osteoarthritis. Biol Chem. 2010;391(5):571–9.PubMedCrossRef
54.
Hou WS, Li W, Keyszer G, Weber E, Levy R, Klein MJ, et al. Comparison of cathepsins K and S expression within the rheumatoid and osteoarthritic synovium. Arthr Rheum. 2002;46:663–74.CrossRef
55.
Hou WS, Li Z, Büttner FH, Bartnik E, Brömme D. Cleavage site specificity of cathepsin K toward cartilage proteoglycans and protease complex formation. Biol Chem. 2003;384(6):891–7.PubMedCrossRef
56.
Dodds RA, Connor JR, Drake FH, Gowen M. Expression of cathepsin K messenger RNA in giant cells and their precursors in human osteoarthritic synovial tissue. Arthr Rheum. 1999;42(8):1588–93.CrossRef
57.
Wilkins RJ, Hall AC. Control of matrix synthesis in isolated bovine chondrocytes by extracellular and intracellular pH. J Cell Physiol. 1995;164:474–81.PubMedCrossRef
58.
Schurigt U, Stopfel N, Hückel M, Pfirschke C, Wiederanders B, Bräuer R. Local expression of matrix metalloproteinases, cathepsins, and their inhibitors during the development of murine antigen-induced arthritis. Arthr Res Ther. 2005;7(1):R174–88.CrossRef
59.
Baugh M, Black D, Westwood P, Kinghorn E, McGregor K, Bruin J, et al. Therapeutic dosing of an orally active, selective cathepsin S inhibitor suppresses disease in models of autoimmunity. J Autoimmun. 2011 Mar 23 (in press).
60.
Beck H, Schwarz G, Schröter CJ, Deeg M, Baier D, Stevanovic S, et al. Cathepsin S and an asparagine-specific endoprotease dominate the proteolytic processing of human myelin basic protein in vitro. Eur J Immunol. 2001;31:3726–36.PubMedCrossRef
61.
Mastronardi FG, Moscarello MA. Molecules affecting myelin stability: a novel hypothesis regarding the pathogenesis of multiple sclerosis. J Neurosci Res. 2005;80(3):301–8.PubMedCrossRef
62.
63.
Haves-Zburof D, Paperna T, Gour-Lavie A, Mandel I, Glass-Marmor L, Miller A. Cathepsins and their endogenous inhibitors Cystatins: expression and modulation in multiple sclerosis. J Cell Mol Med. 2010 Dec 8 [ahead of press].
64.
Cunningham S, Graham C, Hutchinson M, Droogan A, O’Rourke K, Patterson C, et al. Pharmacogenomics of responsiveness to interferon IFN-beta treatment in multiple sclerosis: a genetic screen of 100 type I interferon-inducible genes. Clin Pharmacol Ther. 2005;78(6):635–46.PubMedCrossRef
65.
Grossman I, Avidan N, Singer C, Goldstaub D, Hayardeny L, Eyal E, et al. Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis reveals drug-response markers. Pharmacogenet Genomics. 2007;17(8):657–66.PubMedCrossRef
66.
Abboud RT, Vimalanathan S. Pathogenesis of COPD. Part I. The role of protease-antiprotease imbalance in emphysema. Int J Tuberc Lung Dis. 2008;12(4):361–7.PubMed
67.
Sutherland ER, Cherniack RM. Management of chronic obstructive pulmonary disease. N Engl J Med. 2004;350(26):2689–97.PubMedCrossRef
68.
Russell RE, Thorley A, Culpitt SV, Dodd S, Donnelly LE, Demattos C, et al. Alveolar macrophage-mediated elastolysis: roles of matrix metalloproteinases, cysteine, and serine proteases. Am J Physiol Lung Cell Mol Physiol. 2002;283(4):867–73.
69.
70.
Altiok O, Yasumatsu R, Bingol-Karakoc G, Riese RJ, Stahlman MT, Dwyer W, et al. Imbalance between cysteine proteases and inhibitors in a baboon model of bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2006;173(3):318–26.PubMedCrossRef
71.
Serveau-Avesque C, Martino MF, Hervé-Grépinet V, Hazouard E, Gauthier F, Diot E, et al. Active cathepsins B, H, K, L and S in human inflammatory bronchoalveolar lavage fluids. Biol Cell. 2006;98(1):15–22.PubMed
72.
Wallace AM, Sandford AJ, English JC, Burkett KM, Li H, Finley RJ, et al. Matrix metalloproteinase expression by human alveolar macrophages in relation to emphysema. COPD. 2008;5(1):13–23.PubMedCrossRef
73.
Greene CM, McElvaney NG. Proteases and antiproteases in chronic neutrophilic lung disease—relevance to drug discovery. Br J Pharmacol. 2009;158(4):1048–58.PubMedCrossRef
74.
Martin SL, Moffitt KL, McDowell A, Greenan C, Bright-Thomas RJ, Jones AM, Webb AK, Elborn JS. Association of airway cathepsin B and S with inflammation in cystic fibrosis. Pediatr Pulmonol. 2010;45(9):860–8.PubMedCrossRef
75.
Taggart CC, Greene CM, Smith SG, Levine RL, McCray PB Jr, O’Neill S, et al. Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins. J Immunol. 2003;171(2):931–7.PubMed
76.
Deschamps K, Cromlish W, Weicker S, Lamontagne S, Huszar SL, Gauthier JY, et al. Genetic and pharmacological evaluation of Cathepsin S in a mouse model of asthma. Am J Respir Cell Mol Biol. 2010 Sep 20 (in press).
77.
Wang Z, Zheng T, Zhu Z, Homer RJ, Riese RJ, Chapman HA Jr, et al. Interferon gamma induction of pulmonary emphysema in the adult murine lung. J Exp Med. 2000;192(11):1587–600.PubMedCrossRef
78.
Zheng T, Kang MJ, Crothers K, Zhu Z, Liu W, Lee CG, et al. Role of cathepsin S-dependent epithelial cell apoptosis in IFN-gamma-induced alveolar remodeling and pulmonary emphysema. J Immunol. 2005;174(12):8106–15.PubMed
79.
Zheng T, Zhu Z, Wang Z, Homer RJ, Ma B, Riese RJ Jr, et al. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema. J Clin Invest. 2000;106(9):1081–93.PubMedCrossRef
80.
Taggart CC, Lowe GJ, Greene CM, Mulgrew AT, O’Neill SJ, Levine RL, et al. Cathepsin B, L, and S cleave and inactivate secretory leucoprotease inhibitor. J Biol Chem. 2001;276(36):33345–52.PubMedCrossRef
81.
Geraghty P, Greene CM, O’Mahony M, O’Neill SJ, Taggart CC, McElvaney NG. Secretory leucocyte protease inhibitor inhibits interferon-gamma-induced cathepsin S expression. J Biol Chem. 2007;282(46):33389–95.PubMedCrossRef
82.
Minematsu N, Nakamura H, Furuuchi M, Nakajima T, Takahashi S, Tsujimura S, et al. Common functional polymorphisms in the cathepsin S promoter in Japanese subjects: possible contribution to pulmonary emphysema. Respirology. 2008;13(4):498–504.PubMedCrossRef
83.
Sukhova GK, Shi GP, Simon DI, Chapman HA, Libby P. Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. J Clin Invest. 1998;102(3):576–83.PubMedCrossRef
84.
Liu J, Sukhova GK, Sun JS, Xu WH, Libby P, Shi GP. Lysosomal cysteine proteases in atherosclerosis. Arterioscler Thromb Vasc Biol. 2004;24(8):1359–66.PubMedCrossRef
85.
Sukhova GK, Zhang Y, Pan JH, Wada Y, Yamamoto T, Naito M, et al. Deficiency of cathepsin S reduces atherosclerosis in LDL receptor-deficient mice. J Clin Invest. 2003;111(6):897–906.PubMed
86.
Lafarge JC, Naour N, Clément K, Guerre-Millo M. Cathepsins and cystatin C in atherosclerosis and obesity. Biochimie. 2010;92(11):1580–6.PubMedCrossRef
87.
Rodgers KJ, Watkins DJ, Miller AL, Chan PY, Karanam S, Brissette WH, et al. Destabilizing role of cathepsin S in murine atherosclerotic plaques. Arterioscler Thromb Vasc Biol. 2006;264:851–6.CrossRef
88.
Samokhin AO, Lythgo PA, Gauthier JY, Percival MD, Brömme D. Pharmacological inhibition of cathepsin S decreases atherosclerotic lesions in Apoe−/− mice. J Cardiovasc Pharmacol. 2010;56(1):98–105.PubMedCrossRef
89.
Taleb S, Lacasa D, Bastard JP, Poitou C, Cancello R, Pelloux V, et al. Cathepsin S, a novel biomarker of adiposity: relevance to atherogenesis. FASEB J. 2005;19(11):1540–2.PubMed
90.
Taleb S, Cancello R, Poitou C, Rouault C, Sellam P, Levy P, et al. Weight loss reduces adipose tissue cathepsin S and its circulating levels in morbidly obese women. J Clin Endocrinol Metab. 2006;91(3):1042–7.PubMed
91.
Taleb S, Clément K. Emerging role of cathepsin S in obesity and its associated diseases. Clin Chem Lab Med. 2007;45(3):328–32.PubMedCrossRef
92.
Naour N, Rouault C, Fellahi S, Lavoie ME, Poitou C, Keophiphath M, et al. Cathepsins in human obesity: changes in energy balance predominantly affect cathepsin s in adipose tissue and in circulation. J Clin Endocrinol Metab. 2010;95(4):1861–8.PubMedCrossRef
93.
Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 2010;9(8):807–19.PubMedCrossRef
94.
Liuzzo JP, Petanceska SS, Moscatelli D, Devi LA. Inflammatory mediators regulate cathepsin S in macrophages and microglia: a role in attenuating heparan sulfate interactions. Mol Med. 1999;5(5):320–33.PubMed
95.
Barclay J, Clark AK, Ganju P, Gentry C, Patel S, Wotherspoon G, et al. Role of the cysteine protease cathepsin S in neuropathic hyperalgesia. Pain. 2007;130(3):225–34.PubMedCrossRef
96.
Clark AK, Yip PK, Grist J, Gentry C, Staniland AA, Marchand F, et al. Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain. Proc Natl Acad Sci USA. 2007;104(25):10655–60.PubMedCrossRef
97.
Clark AK, Yip PK, Malcangio M. The liberation of fractalkine in the dorsal horn requires microglial cathepsin S. J Neurosci. 2009;29(21):6945–54.PubMedCrossRef
98.
Abbadiea C, Bhangoob S, De Koninckc Y, Malcangiod M, Melik-Parsadaniantze S, Whitef FA. Chemokines and pain mechanisms. Brain Res Rev. 2009;60(1):125–34.CrossRef
99.
Mohammed MM, Sloane BF. Cysteine cathepsins: multifunctional enzymes in cancer. Nat Rev Cancer. 2006;6(10):764–75.CrossRef
100.
Palermo C, Joyce JA. Cysteine cathepsin proteases as pharmacological targets in cancer. Trends Pharmacol Sci. 2008;29(1):22–8.PubMedCrossRef
101.
Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, et al. The landscape of somatic copy-number alteration across human cancers. Nature. 2010;463(7283):899–905.PubMedCrossRef
102.
Flannery T, Gibson D, Mirakhur M, McQuaid S, Greenan C, Trimble A, et al. The clinical significance of cathepsin S expression in human astrocytomas. Am J Pathol. 2003;163(1):175–82.PubMed
103.
Flannery T, McQuaid S, McGoohan C, McConnell RS, McGregor G, Mirakhur M, et al. Cathepsin S expression: an independent prognostic factor in glioblastoma tumours—a pilot study. Int J Cancer. 2006;119(4):854–60.PubMedCrossRef
104.
Flannery T, McConnell RS, McQuaid S, McGregor G, Mirakhur M, Martin L, et al. Detection of cathepsin S cysteine protease in human brain tumour microdialysates in vivo. Br J Neurosurg. 2007;21(2):204–9.PubMedCrossRef
105.
Fernández PL, Farré X, Nadal A, Fernández E, Peiró N, Sloane BF, et al. Expression of cathepsins B and S in the progression of prostate carcinoma. Int J Cancer. 2001;95(1):51–5.PubMedCrossRef
106.
Lindahl C, Simonsson M, Bergh A, Thysell E, Antti H, Sund M, et al. Increased levels of macrophage-secreted cathepsin S during prostate cancer progression in TRAMP mice and patients. Cancer Genomics Proteomics. 2009;6(3):149–59.PubMed
107.
Paraoan L, Gray D, Hiscott P, Garcia-Finana M, Lane B, Damato B, et al. Cathepsin S and its inhibitor cystatin C: imbalance in uveal melanoma. Front Biosci. 2009;14:2504–13.PubMedCrossRef
108.
Burden RE, Gormley JA, Jaquin TJ, Small DM, Quinn DJ, Hegarty SM, et al. Antibody-mediated inhibition of cathepsin S blocks colorectal tumor invasion and angiogenesis. Clin Cancer Res. 2009;15(19):6042–51.PubMedCrossRef
109.
Kos J, Sekirnik A, Kopitar G, Cimerman N, Kayser K, Stremmer A, et al. Cathepsin S in tumours, regional lymph nodes and sera of patients with lung cancer: relation to prognosis. Br J Cancer. 2001;85(8):1193–200.PubMedCrossRef
110.
Bunatova K, Obermajer N, Kotyza J, Pesek M, Kos J. Levels of cathepsins S and H in pleural fluids of inflammatory and neoplastic origin. Int J Biol Markers. 2009;24(1):47–51.PubMed
111.
Xu J, Li D, Ke Z, Liu R, Maubach G, Zhuo L. Cathepsin S is aberrantly overexpressed in human hepatocellular carcinoma. Mol Med Rep. 2009;2(5):713–8.
112.
Ryschich E, Lizdenis P, Ittrich C, Benner A, Stahl S, Hamann A, et al. Molecular fingerprinting and autocrine growth regulation of endothelial cells in a murine model of hepatocellular carcinoma. Cancer Res. 2006;66(1):198–211.PubMedCrossRef
113.
Shi GP, Sukhova GK, Kuzuya M, Ye Q, Du J, Zhang Y, et al. Deficiency of the cysteine protease cathepsin S impairs microvessel growth. Circ Res. 2003;92:493–500.PubMedCrossRef
114.
Gocheva V, Zeng W, Ke D, Klimstra D, Reinheckel T, Peters C, et al. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev. 2006;20:543–56.PubMedCrossRef
115.
Wang B, Sun J, Kitamoto S, Yang M, Grubb A, Chapman HA, et al. Cathepsin S controls angiogenesis and tumor growth via matrix-derived angiogenic factors. J Biol Chem. 2006;281(9):6020–9.PubMed
116.
Gocheva V, Wang HW, Gadea BB, Shree T, Hunter KE, Garfall AL, et al. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev. 2010;24(3):241–55.PubMedCrossRef
117.
Ward C, Kuehn D, Burden RE, Gormley JA, Jaquin TJ, Gazdoiu M, et al. Antibody targeting of cathepsin S inhibits angiogenesis and synergistically enhances anti-VEGF. PLoS One. 2010;5(9):12543.CrossRef
118.
Gupta S, Singh RK, Dastidar S, Ray A. Cysteine cathepsin S as an immunomodulatory target: present and future trends. Expert Opin Ther Targets. 2008;12(3):291–9.PubMedCrossRef
119.
Brömme D, Bonneau PR, Lachance P, Storer AC. Engineering the S2 subsite specificity of human cathepsin S to a cathepsin L- and cathepsin B-like specificity. J Biol Chem. 1994;269(48):30238–42.PubMed
120.
Pauly TA, Sulea T, Ammirati M, Sivaraman J, Danley DE, Griffor MC, et al. Specificity determinants of human cathepsin s revealed by crystal structures of complexes. Biochemistry. 2003;42(11):3203–13.PubMedCrossRef
121.
Link JO, Zipfel S. Advances in cathepsin S inhibitor design. Curr Opin Drug Discov Dev. 2006;9(4):471–82.
122.
Wiener JJ, Sun S, Thurmond RL. Recent advances in the design of cathepsin S inhibitors. Curr Top Med Chem. 2010;10(7):717–32.PubMedCrossRef
123.
Lee-Dutra A, Wiener DK, Sun S. Cathepsin S inhibitors: 2004–2010. Expert Opin Ther Pat. 2011;21(3):311–37.PubMedCrossRef
124.
Black WC, Percival MD. The consequences of lysosomotropism on the design of selective cathepsin K inhibitors. Chembiochem. 2006;7(10):1525–35.PubMedCrossRef
125.
Gauthier JY, Chauret N, Cromlish W, Desmarais S, Duong le T, Falgueyret JP, et al. The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett. 2008;18(3):923–8.PubMedCrossRef
126.
Rachner TD, Khosla S, Hofbauer LC. Osteoporosis: now and the future. Lancet. 2011;377(9773):1276–87.PubMedCrossRef
127.
Jensen AB, Wynne C, Ramirez G, He W, Song Y, Berd Y, et al. The cathepsin K inhibitor odanacatib suppresses bone resorption in women with breast cancer and established bone metastases: results of a 4-week, double-blind, randomized, controlled trial. Clin Breast Cancer. 2010;10(6):452–8.PubMedCrossRef
128.
Scott CJ, Taggart CC. Biologic protease inhibitors as novel therapeutic agents. BioChimie. 2010;92(11):1681–8.PubMedCrossRef
Metadata
Title
The Emerging Relevance of the Cysteine Protease Cathepsin S in Disease
Authors
Donna M. Small
Roberta E. Burden
Christopher J. Scott
Publication date
01-06-2011
Publisher
Springer-Verlag
Published in
Clinical & Translational Metabolism / Issue 2/2011
Print ISSN: 1534-8644
Electronic ISSN: 2948-2445
DOI
https://doi.org/10.1007/s12018-011-9095-5

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Cysteine Protease Cathepsins in Atherosclerosis and Abdominal Aortic Aneurysm

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Cathepsin L in Normal and Pathological Bone Remodeling

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Cysteine Cathepsins and the Skeleton

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Thyroid Cathepsin K: Roles in Physiology and Thyroid Disease
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