Cathepsin D-Many functions of one aspartic protease

Critical Reviews in Oncology/Hematology

Volumn 68, Issue 1, 2008, Pages 12-28

  Benes, Petr ^a   Vetvicka, Vaclav ^b   Fusek, Martin ^c  

^a MASARYK UNIVERSITY   (Czech Republic)

^b University of Louisville School of Medicine   (United States)

^c INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY   (Czech Republic)

Author keywords

Alzheimer's disease; Apoptosis; Aspartic protease; Atherosclerosis; Cancer; Cathepsin D; Knock out mice; Procathepsin D

Indexed keywords

ANTISENSE OLIGODEOXYNUCLEOTIDE; CANCER VACCINE; CATHEPSIN D; CATHEPSIN D ANTIBODY; CISPLATIN; DOXORUBICIN; ETOPOSIDE; FAS ANTIGEN; FLUOROURACIL; GAMMA INTERFERON; MITOGEN ACTIVATED PROTEIN KINASE; PEPSTATIN; PREPROCATHEPSIN D; PROCATHEPSIN D; PROCATHEPSIN D ANTIBODY; PROTEIN; PROTEIN ANTIBODY; PROTEIN PRECURSOR; PSEUDOCATHEPSIN D; RESVERATROL; RIBOZYME; SMALL INTERFERING RNA; SPHINGOSINE; STAUROSPORINE; TUMOR MARKER; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG;

ACIDITY; ALZHEIMER DISEASE; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ATHEROGENESIS; ATHEROSCLEROSIS; AUTOCRINE EFFECT; BRAIN NERVE CELL; BREAST CANCER; BREAST CARCINOMA; BREAST FEEDING; CANCER CELL; CANCER GENE THERAPY; CANCER GROWTH; CANCER IMMUNIZATION; CANCER INVASION; CANCER PREVENTION; CANCER RISK; CARCINOGENESIS; CELL MEMBRANE; CELL PROLIFERATION; DEVELOPMENTAL DISORDER; DISEASE SEVERITY; DRUG TARGETING; EMBRYO DEVELOPMENT; ENDOPLASMIC RETICULUM; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME INACTIVATION; EPILEPSY; GENE MUTATION; GOLGI COMPLEX; HOMEOSTASIS; HUMAN; KNOCKOUT MOUSE; LEWIS CARCINOMA; LIVER METASTASIS; LUNG CANCER; LUNG METASTASIS; LYSOSOME; METASTASIS; MITOCHONDRIAL RESPIRATION; NEOPLASM; NERVE CELL NECROSIS; NERVE DEGENERATION; NEURONAL CEROID LIPOFUSCINOSIS; NONHUMAN; NUCLEOCYTOPLASMIC TRANSPORT; ORGANOGENESIS; OVARY CANCER; OVARY CARCINOMA; OXIDATIVE STRESS; POSTNATAL DEVELOPMENT; PROGNOSIS; PROSTATE CANCER; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN SECRETION; PROTEIN TARGETING; PROTEIN TRANSPORT; RETINA NERVE CELL; REVIEW; RIBOZYME THERAPY; RISK REDUCTION; RNA INTERFERENCE; SIGNAL TRANSDUCTION; SKIN FUNCTION; VISUAL IMPAIRMENT;

ALZHEIMER DISEASE; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; ATHEROSCLEROSIS; CATHEPSIN D; ENZYME PRECURSORS; HUMANS; ISOENZYMES; MICE; MICE, TRANSGENIC; NEOPLASMS; PROTEASE INHIBITORS; TREATMENT OUTCOME; TUMOR MARKERS, BIOLOGICAL;

EID: 50649106648     PISSN: 10408428     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.critrevonc.2008.02.008     Document Type: Review

References (220)

1. Hasilik A., and Neufeld E.F. Biosynthesis of lysosomal enzymes in fibroblasts. Synthesis as precursors of higher molecular weight. J Biol Chem 255 (1980) 4937-4945
2. Kornfeld S. Lysosomal enzyme targeting. Biochem Soc Trans 18 (1990) 367-374
3. Hasilik A., and Neufeld E.F. Biosynthesis of lysosomal enzymes in fibroblasts. Phosphorylation of mannose residues. J Biol Chem 255 (1980) 4946-4950
4. Fortenberry S.C., Schorey J.S., and Chirgwin J.M. Role of glycosylation in the expression of human procathepsin D. J Cell Sci 108 (1995) 2001-2006
5. von Figura K., and Hasilik A. Lysosomal enzymes and their receptors. Annu Rev Biochem 55 (1986) 167-193
6. Rijnboutt S., Kal A.J., Geuze H.J., Aerts H., and Strous G.J. Mannose 6-phosphate-independent targeting of cathepsin D to lysosomes in HepG2 cells. J Biol Chem 266 (1991) 23586-23592
7. Zhu Y., and Conner G.E. Intermolecular association of lysosomal protein precursors during biosynthesis. J Biol Chem 269 (1994) 3846-3851
8. Capony F., Braulke T., Rougeot C., Roux S., Montcourrier P., and Rochefort H. Specific mannose-6-phosphate receptor-independent sorting of pro-cathepsin D in breast cancer cells. Exp Cell Res 215 (1994) 154-163
9. Dittmer F., Ulbrich E.J., Hafner A., et al. Alternative mechanisms for trafficking of lysosomal enzymes in mannose 6-phosphate receptor-deficient mice are cell type-specific. J Cell Sci 112 (1999) 1591-1597
10. Gopalakrishnan M.M., Grosch H.W., Locatelli-Hoops S., et al. Purified recombinant human prosaposin forms oligomers that bind procathepsin D and affect its autoactivation. Biochem J 383 (2004) 507-515
11. 2-terminal sequences in cathepsin D. J Biol Chem 256 (1981) 11224-11231
12. Conner G.E., and Richo G. Isolation and characterization of a stable activation intermediate of the lysosomal aspartyl protease cathepsin D. Biochemistry 31 (1992) 1142-1147
13. Gieselmann V., Hasilik A., and von Figura K. Processing of human cathepsin D in lysosomes in vitro. J Biol Chem 260 (1985) 3215-3220
14. Hentze M., Hasilik A., and von Figura K. Enhanced degradation of cathepsin D synthesized in the presence of the threonine analog beta-hydroxynorvaline. Arch Biochem Biophys 230 (1984) 375-382
15. Samarel A.M., Ferguson A.G., Decker R.S., and Lesch M. Effects of cysteine protease inhibitors on rabbit cathepsin D maturation. Am J Physiol 257 (1989) 1069-1079
16. Richo G., and Conner G.E. Proteolytic activation of human procathepsin D. Adv Exp Med Biol 306 (1991) 289-296
17. Wittlin S., Rösel J., Hofmann F., and Stover D.R. Mechanisms and kinetics of procathepsin D activation. Eur J Biochem 265 (1999) 384-393
18. Heinrich M., Wickel M., Schneider-Brachert W., et al. Cathepsin D targeted by acid sphingomyelinase-derived ceramide. EMBO J 18 (1999) 5252-5263
19. Eder J., Hommel U., Cumin F., Martoglio B., and Gerhartz B. Aspartic proteases in drug discovery. Curr Pharm Des 13 (2007) 271-285
20. Vetvicka V., Vagner J., Baudys M., Tang J., Foundling S.I., and Fusek M. Human breast milk contains procathepsin D-detection by specific antibodies. Biochem Mol Biol Int 30 (1993) 921-928
21. Larsen L.B., and Petersen T.E. Identification of five molecular forms of cathepsin D in bovine milk. Adv Exp Med Biol 362 (1995) 279-283
22. Benes P., Koelsch G., Dvorak B., Fusek M., and Vetvicka V. Detection of procathepsin D in rat milk. Comp Biochem Physiol B Biochem Mol Biol 133 (2002) 113-118
23. Zühlsdorf M., Imort M., Hasilik A., and von Figura K. Molecular forms of beta-hexosaminidase and cathepsin D in serum and urine of healthy subjects and patients with elevated activity of lysosomal enzymes. Biochem J 213 (1983) 733-740
24. Baechle D., Flad T., Cansier A., et al. Cathepsin D is present in human eccrine sweat and involved in the postsecretory processing of the antimicrobial peptide DCD-1L. J Biol Chem 281 (2006) 5406-5415
25. Leto G., Tumminello F.M., Crescimanno M., Flandina C., and Gebbia N. Cathepsin D expression levels in nongynecological solid tumors: clinical and therapeutic implications. Clin Exp Metastasis 21 (2004) 91-106
26. Laurent-Matha V., Farnoud M.R., Lucas A., Rougeot C., Garcia M., and Rochefort H. Endocytosis of pro-cathepsin D into breast cancer cells is mostly independent of mannose-6-phosphate receptors. J Cell Sci 111 (1998) 2539-2549
27. Laurent-Matha V., Maruani-Herrmann S., Prébois C., et al. Catalytically inactive human cathepsin D triggers fibroblast invasive growth. J Cell Biol 168 (2005) 489-499
28. Poole A.R., Hembry R.M., and Dingle J.T. Cathepsin D in cartilage: the immunohistochemical demonstration of extracellular enzyme in normal and pathological conditions. J Cell Sci 14 (1974) 139-161
29. Poole A.R., Hembry R.M., Dingle J.T., Pinder I., Ring E.F., and Cosh J. Secretion and localization of cathepsin D in synovial tissues removed from rheumatoid and traumatized joints. An immunohistochemical study. Arthritis Rheum 19 (1976) 1295-1307
30. Bjelle A., and Osterlin S. Cathepsin D activity in bovine articular cartilage, synovial membrane and fluid: degradation of cartilage proteoglycans from same joint. J Rheumatol 3 (1976) 400-408
31. Vittorio N., Crissman J.D., Hopson C.N., and Herman J.H. Histologic assessment of cathepsin D in osteoarthritic cartilage. Clin Exp Rheumatol 4 (1986) 221-230
32. Hakala J.K., Oksjoki R., Laine P., et al. Lysosomal enzymes are released from cultured human macrophages, hydrolyze LDL in vitro, and are present extracellularly in human atherosclerotic lesions. Arterioscler Thromb Vasc Biol 23 (2003) 1430-1436
33. Vashishta A., Saraswat Ohri S., Vetvickova J., Fusek M., Ulrichova J., and Vetvicka V. Procathepsin D secreted by HaCaT keratinocyte cells-a novel regulator of keratinocyte growth. Eur J Cell Biol 86 (2007) 303-313
34. Dunn B.M., Scarborough P.E., Lowther W.T., and Rao-Naik C. Comparison of the active site specificity of the aspartic proteinases based on a systematic series of peptide substrates. Adv Exp Med Biol 362 (1995) 1-9
35. Dunn B.M., and Hung S. The two sides of enzyme-substrate specificity: lessons from the aspartic proteinases. Biochim Biophys Acta 1477 (2000) 231-240
36. Bankowska A., Gacko M., Chyczewska E., and Worowska A. Biological and diagnostic role of cathepsin D. Rocz Akad Med Bialymst 42 Suppl. 1 (1997) 79-85
37. Takei Y., Higashira H., Yamamoto T., and Hayashi K. Mitogenic activity toward human breast cancer cell line MCF-7 of two bFGFs purified from sera of breast cancer patients: co-operative role of cathepsin D. Breast Cancer Res Treat 43 (1997) 53-63
38. Morikawa W., Yamamoto K., Ishikawa S., et al. Angiostatin generation by cathepsin D secreted by human prostate carcinoma cells. J Biol Chem 275 (2000) 38912-38920
39. Piwnica D., Touraine P., Struman I., et al. Cathepsin D processes human prolactin into multiple 16K-like N-terminal fragments: study of their antiangiogenic properties and physiological relevance. Mol Endocrinol 18 (2004) 2522-2542
40. Lkhider M., Castino R., Bouguyon E., Isidoro C., and Ollivier-Bousquet M. Cathepsin D released by lactating rat mammary epithelial cells is involved in prolactin cleavage under physiological conditions. J Cell Sci 117 (2004) 5155-5164
41. Ferreras M., Felbor U., Lenhard T., Olsen B.R., and Delaissé J. Generation and degradation of human endostatin proteins by various proteinases. FEBS Lett 486 (2000) 247-251
42. Baumgrass R., Williamson M.K., and Price P.A. Identification of peptide fragments generated by digestion of bovine and human osteocalcin with the lysosomal proteinases cathepsin B, D, L, H, and S. J Bone Miner Res 12 (1997) 447-455
43. Dunn A.D., Crutchfield H.E., and Dunn J.T. Thyroglobulin processing by thyroidal proteases. Major sites of cleavage by cathepsins B, D, and L. J Biol Chem 266 (1991) 20198-20204
44. Woessner Jr. J.F., and Shamberger Jr. R.J. Purification and properties of cathepsin D from bovine utrus. J Biol Chem 246 (1971) 1951-1960
45. Authier F., Mort J.S., Bell A.W., Posner B.I., and Bergeron J.J. Proteolysis of glucagon within hepatic endosomes by membrane-associated cathepsins B and D. J Biol Chem 270 (1995) 15798-15807
46. Kudo S., Miyamoto G., and Kawano K. Proteases involved in the metabolic degradation of human interleukin-1beta by rat kidney lysosomes. J Interferon Cytokine Res 19 (1999) 361-367
47. Nunn S.E., Peehl D.M., and Cohen P. Acid-activated insulin-like growth factor binding protein protease activity of cathepsin D in normal and malignant prostatic epithelial cells and seminal plasma. J Cell Physiol 171 (1997) 196-204
48. Mordente J.A., Choudhury M.S., Tazaki H., Mallouh C., and Konno S. Hydrolysis of androgen receptor by cathepsin D: its biological significance in human prostate cancer. Br J Urol 82 (1998) 431-435
49. Diment S., Martin K.J., and Stahl P.D. Cleavage of parathyroid hormone in macrophage endosomes illustrates a novel pathway for intracellular processing of proteins. J Biol Chem 264 (1989) 13403-13406
50. Wolf M., Clark-Lewis I., Buri C., Langen H., Lis M., and Mazzucchelli L. 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 (2003) 1183-1190
51. Nishimura Y., Kawabata T., and Kato K. Identification of latent procathepsins B and L in microsomal lumen: characterization of enzymatic activation and proteolytic processing in vitro. Arch Biochem Biophys 261 (1988) 64-71
52. van der Stappen J.W., Williams A.C., Maciewicz R.A., and Paraskeva C. Activation of cathepsin B, secreted by a colorectal cancer cell line requires low pH and is mediated by cathepsin D. Int J Cancer 67 (1996) 547-554
53. Nishimura Y., Kawabata T., Furuno K., and Kato K. Evidence that aspartic proteinase is involved in the proteolytic processing event of procathepsin L in lysosomes. Arch Biochem Biophys 271 (1989) 400-406
54. Egberts F., Heinrich M., Jensen J.M., et al. Cathepsin D is involved in the regulation of transglutaminase 1 and epidermal differentiation. J Cell Sci 117 (2004) 2295-2307
55. Sadik G., Kaji H., Takeda K., et al. In vitro processing of amyloid precursor protein by cathepsin D. Int J Biochem Cell Biol 31 (1999) 1327-1337
56. Ladror U.S., Snyder S.W., Wang G.T., Holzman T.F., and Krafft G.A. Cleavage at the amino and carboxyl termini of Alzheimer's amyloid-beta by cathepsin D. J Biol Chem 269 (1994) 18422-18428
57. Kenessey A., Nacharaju P., Ko L.W., and Yen S.H. Degradation of tau by lysosomal enzyme cathepsin D: implication for Alzheimer neurofibrillary degeneration. J Neurochem 69 (1997) 2026-2038
58. Banay-Schwartz M., Bracco F., DeGuzman T., and Lajtha A. Developmental changes in the breakdown of brain tubulin by cerebral cathepsin D. Neurochem Res 8 (1983) 51-61
59. Benuck M., Marks N., and Hashim G.A. Metabolic instability of myelin proteins. Breakdown of basic protein induced by brain cathepsin D. Eur J Biochem 52 (1975) 615-621
60. Kim Y.J., Sapp E., Cuiffo B.G., et al. Lysosomal proteases are involved in generation of N-terminal huntingtin fragments. Neurobiol Dis 22 (2006) 346-356
61. Zhou W., Scott S.A., Shelton S.B., and Crutcher K.A. Cathepsin D-mediated proteolysis of apolipoprotein E: possible role in Alzheimer's disease. Neuroscience 143 (2006) 689-701
62. Takahashi M., Ko L.W., Kulathingal J., Jiang P., Sevlever D., and Yen S.H. Oxidative stress-induced phosphorylation, degradation and aggregation of alpha-synuclein are linked to upregulated CK2 and cathepsin D. Eur J Neurosci 26 (2007) 863-874
63. Banay-Schwartz M., Dahl D., Hui K.S., and Lajtha A. The breakdown of the individual neurofilament proteins by cathepsin D. Neurochem Res 12 (1987) 361-367
64. Bird J.W., Schwartz W.N., and Spanier A.M. Degradation of myofibrillar proteins by cathepsins B and D. Acta Biol Med Ger 36 (1977) 1587-1604
65. Jones T.L., Ogunro E.A., Samarel A.M., Ferguson A.G., and Lesch M. Susceptibilities of cardiac myofibrillar proteins to cathepsin D-catalyzed degradation. Am J Physiol 245 (1983) 294-299
66. Okitani A., Matsumoto T., Kitamura Y., and Kato H. Purification of cathepsin D from rabbit skeletal muscle and its action towards myofibrils. Biochim Biophys Acta 662 (1981) 202-209
67. Simon D.I., Ezratty A.M., and Loscalzo J. The fibrin(ogen)olytic properties of cathepsin D. Biochemistry 33 (1994) 6555-6563
68. Loscalzo J. The macrophage and fibrinolysis. Semin Thromb Hemost 22 (1996) 503-506
69. Heinrich M., Neumeyer J., Jakob M., et al. Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation. Cell Death Differ 11 (2004) 550-563
70. 2 stimulate degradation of thioredoxin-1: implication for endothelial cell apoptosis. J Biol Chem 280 (2005) 42945-42951
71. Hiraiwa M., Martin B.M., Kishimoto Y., Conner G.E., Tsuji S., and O'Brien J.S. Lysosomal proteolysis of prosaposin, the precursor of saposins (sphingolipid activator proteins): its mechanism and inhibition by ganglioside. Arch Biochem Biophys 341 (1997) 17-24
72. Pimenta D.C., Chen V.C., Chao J., Juliano M.A., and Juliano L. Alpha1-antichymotrypsin and kallistatin hydrolysis by human cathepsin D. J Protein Chem 19 (2000) 411-418
73. Lenarcic B., Krasovec M., Ritonja A., Olafsson I., and Turk V. Inactivation of human cystatin C and kininogen by human cathepsin D. FEBS Lett 280 (1991) 211-215
74. van der Westhuyzen D.R., Gevers W., and Coetzee G.A. Cathepsin-D-dependent initiation of the hydrolysis by lysosomal enzymes of apoprotein B from low-density lipoproteins. Eur J Biochem 112 (1980) 153-160
75. Roughley P.J. The degradation of cartilage proteoglycans by tissue proteinases. Proteoglycan heterogeneity and the pathway of proteolytic degradation. Biochem J 167 (1977) 639-646
76. Handley C.J., Mok M.T., Ilic M.Z., Adcocks C., Buttle D.J., and Robinson H.C. Cathepsin D cleaves aggrecan at unique sites within the interglobular domain and chondroitin sulfate attachment regions that are also cleaved when cartilage is maintained at acid pH. Matrix Biol 20 (2001) 543-553
77. Scott P.G., and Pearson C.H. Cathepsin D: cleavage of soluble collagen and crosslinked peptides. FEBS Lett 88 (1978) 41-45
78. Scott P.G., and Pearson H. Cathepsin D: specificity of peptide-bond cleavage in type-I collagen and effects on type-III collagen and procollagen. Eur J Biochem 114 (1981) 59-62
79. Tressel T., Shively J.E., and Pande H. Human placental fibronectin: demonstration of structural differences between the A and B chains in the extra domain-A region. Arch Biochem Biophys 266 (1988) 639-643
80. Hultquist D.E., Rodriguez C., and Schafer D.A. Cathepsin D in erythroid cells. Prog Clin Biol Res 319 (1989) 93-101
81. Kim K., Homma Y., Ikeuchi Y., and Suzuki A. Cleavage of connectin by calpain and cathepsin D. Biosci Biotechnol Biochem 59 (1995) 896-899
82. Saftig P., Hetman M., Schmahl W., et al. Mice deficient for the lysosomal proteinase cathepsin D exhibit progressive atrophy of the intestinal mucosa and profound destruction of lymphoid cells. EMBO J 14 (1995) 3599-3608
83. Guicciardi M.E., Leist M., and Gores G.J. Lysosomes in cell death. Oncogene 23 (2004) 2881-2890
84. Koike M., Shibata M., Ohsawa Y., et al. Involvement of two different cell death pathways in retinal atrophy of cathepsin D-deficient mice. Mol Cell Neurosci 22 (2003) 146-161
85. Myllykangas L., Tyynelä J., Page-McCaw A., Rubin G.M., Haltia M.J., and Feany M.B. Cathepsin D-deficient Drosophila recapitulate the key features of neuronal ceroid lipofuscinoses. Neurobiol Dis 19 (2005) 194-199
86. Tyynelä J., Sohar I., Sleat D.E., et al. A mutation in the ovine cathepsin D gene causes a congenital lysosomal storage disease with profound neurodegeneration. EMBO J 19 (2000) 2786-2792
87. Tyynelä J., Sohar I., Sleat D.E., et al. Congenital ovine neuronal ceroid lipofuscinosis-a cathepsin D deficiency with increased levels of the inactive enzyme. Eur J Paediatr Neurol 5 Suppl. A (2001) 43-45
88. Awano T., Katz M.L., O'Brien D.P., et al. A mutation in the cathepsin D gene (CTSD) in American Bulldogs with neuronal ceroid lipofuscinosis. Mol Genet Metab 87 (2006) 341-348
89. Steinfeld R., Reinhardt K., Schreiber K., et al. Cathepsin D deficiency is associated with a human neurodegenerative disorder. Am J Hum Genet 78 (2006) 988-998
90. Siintola E., Partanen S., Strömme P., et al. Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis. Brain 129 (2006) 1438-1445
91. Partanen S., Storch S., Löffler H.G., Hasilik A., Tyynelä J., and Braulke T. A replacement of the active-site aspartic acid residue 293 in mouse cathepsin D affects its intracellular stability, processing and transport in HEK-293 cells. Biochem J 369 (2003) 55-62
92. Koike M., Nakanishi H., Saftig P., et al. Cathepsin D deficiency induces lysosomal storage with ceroid lipofuscin in mouse CNS neurons. J Neurosci 20 (2000) 6898-6906
93. Koike M., Shibata M., Waguri S., et al. Participation of autophagy in storage of lysosomes in neurons from mouse models of neuronal ceroid-lipofuscinoses (Batten disease). Am J Pathol 167 (2005) 1713-1728
94. Walls K.C., Klocke B.J., Saftig P., et al. Altered regulation of phosphatidylinositol 3-kinase signaling in cathepsin D-deficient brain. Autophagy 3 (2007) 222-229
95. Shacka J.J., Klocke B.J., Young C., et al. Cathepsin D deficiency induces persistent neurodegeneration in the absence of Bax-dependent apoptosis. J Neurosci 27 (2007) 2081-2090
96. Zhang D., Brankov M., Makhija M.T., et al. Correlation between inactive cathepsin D expression and retinal changes in mcd2/mcd2 transgenic mice. Invest Ophthalmol Vis Sci 46 (2005) 3031-3038
97. Chen S.H., Arany I., Apisarnthanarax N., et al. Response of keratinocytes from normal and psoriatic epidermis to interferon-gamma differs in the expression of zinc-alpha(2)-glycoprotein and cathepsin D. FASEB J 14 (2000) 565-571
98. Kawada A., Hara K., Kominami E., Hiruma M., Noguchi H., and Ishibashi A. Processing of cathepsins L, B and D in psoriatic epidermis. Arch Dermatol Res 289 (1997) 87-93
99. Kim S.Y., Chung S.I., Yoneda K., and Steinert P.M. Expression of transglutaminase 1 in human epidermis. J Invest Dermatol 104 (1995) 211-217
100. Negi M., Matsui T., and Ogawa H. Mechanism of regulation of human epidermal transglutaminase. J Invest Dermatol 77 (1981) 389-392
101. Negi M., Park J.K., and Ogawa H. Alteration of human epidermal transglutaminase during its activation. J Dermatol Sci 1 (1990) 167-171
102. Steinert P.M., Chung S.I., and Kim S.Y. Inactive zymogen and highly active proteolytically processed membrane-bound forms of the transglutaminase 1 enzyme in human epidermal keratinocytes. Biochem Biophys Res Commun 221 (1996) 101-106
103. Kim S.Y., and Bae C.D. Calpain inhibitors reduce the cornified cell envelope formation by inhibiting proteolytic processing of transglutaminase 1. Exp Mol Med 30 (1998) 257-262
104. Bröker L.E., Kruyt F.A., and Giaccone G. Cell death independent of caspases: a review. Clin Cancer Res 11 (2005) 3155-3162
105. Li W., Yuan X., Nordgren G., et al. Induction of cell death by the lysosomotropic detergent MSDH. FEBS Lett 470 (2000) 35-39
106. Boya P., Gonzalez-Polo R.A., Poncet D., et al. Mitochondrial membrane permeabilization is a critical step of lysosome-initiated apoptosis induced by hydroxychloroquine. Oncogene 22 (2003) 3927-3936
107. Boya P., Andreau K., Poncet D., et al. Lysosomal membrane permeabilization induces cell death in a mitochondrion-dependent fashion. J Exp Med 197 (2003) 1323-1334
108. Bidère N., Lorenzo H.K., Carmona S., et al. Cathepsin D triggers Bax activation, resulting in selective apoptosis-inducing factor (AIF) relocation in T lymphocytes entering the early commitment phase to apoptosis. J Biol Chem 278 (2003) 31401-31411
109. Roberg K., and Ollinger K. Oxidative stress causes relocation of the lysosomal enzyme cathepsin D with ensuing apoptosis in neonatal rat cardiomyocytes. Am J Pathol 152 (1998) 1151-1156
110. Persson H.L., Yu Z., Tirosh O., Eaton J.W., and Brunk U.T. Prevention of oxidant-induced cell death by lysosomotropic iron chelators. Free Radic Biol Med 34 (2003) 1295-1305
111. Castino R., Bellio N., Nicotra G., Follo C., Trincheri N.F., and Isidoro C. Cathepsin D-Bax death pathway in oxidative stressed neuroblastoma cells. Free Radic Biol Med 42 (2007) 1305-1316
112. Kagedal K., Johansson A.C., Johansson U., et al. Lysosomal membrane permeabilization during apoptosis-involvement of Bax?. Int J Exp Pathol 86 (2005) 309-321
113. Kagedal K., Zhao M., Svensson I., and Brunk U.T. Sphingosine-induced apoptosis is dependent on lysosomal proteases. Biochem J 359 (2001) 335-343
114. Zhao M., Antunes F., Eaton J.W., and Brunk U.T. Lysosomal enzymes promote mitochondrial oxidant production, cytochrome c release and apoptosis. Eur J Biochem 270 (2003) 3778-3786
115. Kolesnick R., and Hannun Y.A. Ceramide and apoptosis. Trends Biochem Sci 24 (1999) 224-225
116. Hannun Y.A., and Luberto C. Ceramide in the eukaryotic stress response. Trends Cell Biol 10 (2000) 73-80
117. De Stefanis D., Reffo P., Bonelli G., et al. Increase in ceramide level alters the lysosomal targeting of cathepsin D prior to onset of apoptosis in HT-29 colon cancer cells. Biol Chem 383 (2002) 989-999
118. Deiss L.P., Galinka H., Berissi H., Cohen O., and Kimchi A. Cathepsin D protease mediates programmed cell death induced by interferon-gamma, Fas/APO-1 and TNF-alpha. EMBO J 15 (1996) 3861-3870
119. Roberg K., Kagedal K., and Ollinger K. Microinjection of cathepsin d induces caspase-dependent apoptosis in fibroblasts. Am J Pathol 161 (2002) 89-96
120. Schestkowa O., Geisel D., Jacob R., and Hasilik A. The catalytically inactive precursor of cathepsin D induces apoptosis in human fibroblasts and HeLa cells. J Cell Biochem 101 (2007) 1558-1566
121. Emert-Sedlak L., Shangary S., Rabinovitz A., Miranda M.B., Delach S.M., and Johnson D.E. Involvement of cathepsin D in chemotherapy-induced cytochrome c release, caspase activation, and cell death. Mol Cancer Ther 4 (2005) 733-742
122. Wu G.S., Saftig P., Peters C., and El-Deiry W.S. Potential role for cathepsin D in p53-dependent tumor suppression and chemosensitivity. Oncogene 16 (1998) 2177-2183
123. Trincheri N.F., Nicotra G., Follo C., Castino R., and Isidoro C. Resveratrol induces cell death in colorectal cancer cells by a novel pathway involving lysosomal cathepsin D. Carcinogenesis 28 (2007) 922-931
124. Beaujouin M., Baghdiguian S., Glondu-Lassis M., Berchem G., and Liaudet-Coopman E. Overexpression of both catalytically-active and -inactive cathepsin D by cancer cells enhances apoptosis-dependent chemo-sensitivity. Oncogene 25 (2006) 1967-1973
125. Shibata M., Kanamori S., Isahara K., et al. Participation of cathepsins B and D in apoptosis of PC12 cells following serum deprivation. Biochem Biophys Res Commun 251 (1998) 199-203
126. Roberg K., Johansson U., and Ollinger K. Lysosomal release of cathepsin D precedes relocation of cytochrome c and loss of mitochondrial transmembrane potential during apoptosis induced by oxidative stress. Free Radic Biol Med 27 (1999) 1228-1237
127. Kagedal K., Johansson U., and Ollinger K. The lysosomal protease cathepsin D mediates apoptosis induced by oxidative stress. FASEB J 15 (2001) 1592-1594
128. Tardy C., Tyynelä J., Hasilik A., Levade T., and Andrieu-Abadie N. Stress-induced apoptosis is impaired in cells with a lysosomal targeting defect but is not affected in cells synthesizing a catalytically inactive cathepsin D. Cell Death Differ 10 (2003) 1090-1100
129. Reiners Jr. J.J., Caruso J.A., Mathieu P., Chelladurai B., Yin X.M., and Kessel D. Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves Bid cleavage. Cell Death Differ 9 (2002) 934-944
130. Berchem G., Glondu M., Gleizes M., et al. Cathepsin-D affects multiple tumor progression steps in vivo: proliferation, angiogenesis and apoptosis. Oncogene 21 (2002) 5951-5955
131. Zaidi N., Burster T., Sommandas V., et al. A novel cell penetrating aspartic protease inhibitor blocks processing and presentation of tetanus toxoid more efficiently than pepstatin A. Biochem Biophys Res Commun 364 (2007) 243-249
132. Bessodes M., Antonakis K., Herscovici J., et al. Inhibition of cathepsin D by tripeptides containing statine analogs. Biochem Pharmacol (1999) 58329-58333
133. Yoshida H., Okamoto K., Iwamoto T., et al. Pepstatin A, an aspartic proteinase inhibitor, suppresses RANKL-induced osteoclast differentiation. J Biochem 139 (2006) 583-590
134. Schotte P., Declercq W., Van Huffel S., Vandenabeele P., and Beyaert R. Non-specific effects of methyl ketone peptide inhibitors of caspases. FEBS Lett 442 (1999) 117-121
135. Dash C., Kulkarni A., Dunn B., and Rao M. Aspartic peptidase inhibitors: implications in drug development. Crit Rev Biochem Mol Biol 38 (2003) 89-119
136. Selkoe D.J. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 81 (2001) 741-766
137. Cataldo A.M., Paskevich P.A., Kominami E., and Nixon R.A. Lysosomal hydrolases of different classes are abnormally distributed in brains of patients with Alzheimer disease. Proc Natl Acad Sci USA 88 (1991) 10998-11002
138. Cataldo A.M., Barnett J.L., Berman S.A., et al. Gene expression and cellular content of cathepsin D in Alzheimer's disease brain: evidence for early up-regulation of the endosomal-lysosomal system. Neuron 14 (1995) 671-680
139. Cataldo A.M., and Nixon R.A. Enzymatically active lysosomal proteases are associated with amyloid deposits in Alzheimer brain. Proc Natl Acad Sci USA 87 (1990) 3861-3865
140. Schwagerl A.L., Mohan P.S., Cataldo A.M., Vonsattel J.P., Kowall N.W., and Nixon R.A. Elevated levels of the endosomal-lysosomal proteinase cathepsin D in cerebrospinal fluid in Alzheimer disease. J Neurochem 64 (1995) 443-446
141. Ginsberg S.D., Hemby S.E., Lee V.M., Eberwine J.H., and Trojanowski J.Q. Expression profile of transcripts in Alzheimer's disease tangle-bearing CA1 neurons. Ann Neurol 48 (2000) 77-87
142. Spires T.L., and Hyman B.T. Transgenic models of Alzheimer's disease: learning from animals. NeuroRx 2 (2005) 423-437
143. Saftig P., Peters C., von Figura K., Craessaerts K., Van Leuven F., and De Strooper B. Amyloidogenic processing of human amyloid precursor protein in hippocampal neurons devoid of cathepsin D. J Biol Chem 271 (1996) 27241-27244
144. Touitou I., Capony F., Brouillet J.P., and Rochefort H. Missense polymorphism (C/T224) in the human cathepsin D pro-fragment determined by polymerase chain reaction-single strand conformational polymorphism analysis and possible consequences in cancer cells. Eur J Cancer 30A (1994) 390-394
145. Masa M., Maresova L., Vondrasek J.R., Horn M., Jezek J., and Mares M. Cathepsin d propeptide: mechanism and regulation of its interaction with the catalytic core. Biochemistry 45 (2006) 15474-15482
146. Mariani E., Seripa D., Ingegni T., et al. Interaction of CTSD and A2M polymorphisms in the risk for Alzheimer's disease. J Neurol Sci 247 (2006) 187-191
147. Heun R., Ptok U., Kölsch H., Maier W., and Jessen F. Contribution of apolipoprotein E and cathepsin D genotypes to the familial aggregation of Alzheimer's disease. Dement Geriatr Cogn Disord 18 (2004) 151-158
148. Papassotiropoulos A., Bagli M., Kurz A., et al. A genetic variation of cathepsin D is a major risk factor for Alzheimer's disease. Ann Neurol 47 (2000) 399-403
149. Papassotiropoulos A., Lewis H.D., Bagli M., et al. Cerebrospinal fluid levels of beta-amyloid(42) in patients with Alzheimer's disease are related to the exon 2 polymorphism of the cathepsin D gene. Neuroreport 13 (2002) 1291-1294
150. Riemenschneider M., Blennow K., Wagenpfeil S., et al. The cathepsin D rs17571 polymorphism: effects on CSF tau concentrations in Alzheimer disease. Hum Mutat 27 (2006) 532-537
151. Davidson Y., Gibbons L., Pritchard A., et al. Genetic associations between cathepsin D exon 2 C → T polymorphism and Alzheimer's disease, and pathological correlations with genotype. J Neurol Neurosurg Psychiatry 77 (2006) 515-517
152. Ntais C., Polycarpou A., and Ioannidis J.P. Meta-analysis of the association of the cathepsin D Ala224Val gene polymorphism with the risk of Alzheimer's disease: a HuGE gene-disease association review. Am J Epidemiol 159 (2004) 527-536
153. Bertram L, McQueen M, Mullin K, Blacker D, Tanzi R. The AlzGene database. Alzheimer research forum. Available at: http://www.alzforum.org/res/com/gen/alzgene/meta.asp?geneID=42. Accessed September 20th; 2007.
154. Lusis A.J. Atherosclerosis. Nature 407 (2000) 233-241
155. Duran M.C., Martin-Ventura J.L., Mohammed S., et al. Atorvastatin modulates the profile of proteins released by human atherosclerotic plaques. Eur J Pharmacol 562 (2007) 119-129
156. Leake D.S. Does an acidic pH explain why low density lipoprotein is oxidised in atherosclerotic lesions?. Atherosclerosis 129 (1997) 149-157
157. Tapper H., and Sundler R. Cytosolic pH regulation in mouse macrophages. Proton extrusion by plasma-membrane-localized H(+)-ATPase. Biochem J 281 (1992) 245-250
158. Chen G.C., Lau K., Hamilton R.L., and Kane J.P. Differences in local conformation in human apolipoprotein B-100 of plasma low density and very low density lipoproteins as identified by cathepsin D. J Biol Chem 266 (1991) 12581-12587
159. Chen G.C., Liu W., Duchateau P., et al. Conformational differences in human apolipoprotein B-100 among subspecies of low density lipoproteins (LDL). Association of altered proteolytic accessibility with decreased receptor binding of LDL subspecies from hypertriglyceridemic subjects. J Biol Chem 269 (1994) 29121-29128
160. Björkerud S., and Björkerud B. Apoptosis is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells), and may contribute to the accumulation of gruel and plaque instability. Am J Pathol 149 (1996) 367-380
161. Yuan X.M., Li W., Olsson A.G., and Brunk U.T. The toxicity to macrophages of oxidized low-density lipoprotein is mediated through lysosomal damage. Atherosclerosis 133 (1997) 153-161
162. Hardwick S.J., Hegyi L., Clare K., et al. Apoptosis in human monocyte-macrophages exposed to oxidized low density lipoprotein. J Pathol 179 (1996) 294-302
163. Mitchinson M.J., Ball R.Y., Carpenter K.H., Enright J.H., and Brabbs C.E. Ceroid, macrophages and atherosclerosis. Biochem Soc Trans 18 (1990) 1066-1069
164. Li W., Yuan X.M., and Brunk U.T. OxLDL-induced macrophage cytotoxicity is mediated by lysosomal rupture and modified by intralysosomal redox-active iron. Free Radic Res 29 (1998) 389-398
165. Li W., and Yuan X.M. Increased expression and translocation of lysosomal cathepsins contribute to macrophage apoptosis in atherogenesis. Ann N Y Acad Sci 1030 (2004) 427-433
166. Haidar B., Kiss R.S., Sarov-Blat L., et al. Cathepsin D, a lysosomal protease, regulates ABCA1-mediated lipid efflux. J Biol Chem 281 (2006) 39971-39981
167. Reid W.A., Valler M.J., and Kay J. Immunolocalization of cathepsin D in normal and neoplastic human tissues. J Clin Pathol 39 (1986) 1323-1330
168. Thorpe S.M., Rochefort H., Garcia M., et al. Association between high concentrations of Mr 52,000 cathepsin D and poor prognosis in primary human breast cancer. Cancer Res 49 (1989) 6008-6014
169. Spyratos F., Maudelonde T., Brouillet J.P., et al. Cathepsin D: an independent prognostic factor for metastasis of breast cancer. Lancet 2 (1989) 1115-1118
170. Ioachin E. Immunohistochemical tumour markers in endometrial carcinoma. Eur J Gynaecol Oncol 26 (2005) 363-371
171. Cunat S., Hoffmann P., and Pujol P. Estrogens and epithelial ovarian cancer. Gynecol Oncol 94 (2004) 25-32
172. Rochefort H., and Liaudet-Coopman E. Cathepsin D in cancer metastasis: a protease and a ligand. APMIS 107 (1999) 86-95
173. Mirza A.N., Mirza N.Q., Vlastos G., and Singletary S.E. Prognostic factors in node-negative breast cancer: a review of studies with sample size more than 200 and follow-up more than 5 years. Ann Surg 235 (2002) 10-26
174. Ferrandina G., Scambia G., Bardelli F., et al. Relationship between
175. Foekens J.A., Look M.P., Bolt-de Vries J., Meijer-van Gelder M.E., van Putten W.L., and Klijn J.G. Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patients. Br J Cancer 79 (1999) 300-307
176. Billgren A.M., Rutqvist L.E., Johansson H., Hägerström T., and Skoog L. The role of cathepsin D and PAI-1 in primary invasive breast cancer as prognosticators and predictors of treatment benefit with adjuvant tamoxifen. Eur J Cancer 36 (2000) 1374-1380
177. Rodríguez J., Vázquez J., Corte M.D., et al. Clinical significance of cathepsin D concentration in tumor cytosol of primary breast cancer. Int J Biol Markers 20 (2005) 103-111
178. Harris L., Fritsche H., Mennel R., et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 25 (2007) 5287-5312
179. Vignon F., Capony F., Chambon M., Freiss G., Garcia M., and Rochefort H. Autocrine growth stimulation of the MCF 7 breast cancer cells by the estrogen-regulated 52 K protein. Endocrinology 118 (1986) 1537-1545
180. Fusek M., and Vetvicka V. Mitogenic function of human procathepsin D: the role of the propeptide. Biochem J 303 (1994) 775-780
181. Vetvicka V., Vetvickova J., and Fusek M. Effect of human procathepsin D on proliferation of human cell lines. Cancer Lett 79 (1994) 131-135
182. Vetvicka V., Vetvickova J., and Fusek M. Effect of procathepsin D and its activation peptide on prostate cancer cells. Cancer Lett 129 (1998) 55-59
183. Vetvicka V., Vetvickova J., and Fusek M. Role of procathepsin D activation peptide in prostate cancer growth. Prostate 44 (2000) 1-7
184. Bazzett L.B., Watkins C.S., Gercel-Taylor C., and Taylor D.D. Modulation of proliferation and chemosensitivity by procathepsin D and its peptides in ovarian cancer. Gynecol Oncol 74 (1999) 181-187
185. Vetvicka V., Vetvickova J., and Benes P. Role of enzymatically inactive procathepsin D in lung cancer. Anticancer Res 24 (2004) 2739-2743
186. Vashishta A., Ohri S.S., Proctor M., Fusek M., and Vetvicka V. Role of activation peptide of procathepsin D in proliferation and invasion of lung cancer cells. Anticancer Res 26 (2006) 4163-4170
187. Glondu M., Liaudet-Coopman E., Derocq D., Platet N., Rochefort H., and Garcia M. Down-regulation of cathepsin-D expression by antisense gene transfer inhibits tumor growth and experimental lung metastasis of human breast cancer cells. Oncogene 21 (2002) 5127-5134
188. Ohri S.S., Vashishta A., Proctor M., Fusek M., and Vetvicka V. Depletion of procathepsin D gene expression by RNA interference: a potential therapeutic target for breast cancer. Cancer Biol Ther 6 (2007) 1081-1087
189. Vashishta A., Ohri S.S., Proctor M., Fusek M., and Vetvicka V. 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 (2007) 1223-1230
190. Vetvicka V., Vetvickova J., Hilgert I., Voburka Z., and Fusek M. Analysis of the interaction of procathepsin D activation peptide with breast cancer cells. Int J Cancer 73 (1997) 403-409
191. Vetvicka V., Vetvickova J., and Fusek M. Anti-human procathepsin D activation peptide antibodies inhibit breast cancer development. Breast Cancer Res Treat 57 (1999) 261-269
192. Gerweck L.E., and Seetharaman K. Cellular pH gradient in tumor versus normal tissue: potential exploitation for the treatment of cancer. Cancer Res 56 (1996) 1194-1198
193. Montcourrier P., Silver I., Farnoud R., Bird I., and Rochefort H. Breast cancer cells have a high capacity to acidify extracellular milieu by a dual mechanism. Clin Exp Metastasis 15 (1997) 382-392
194. Glondu M., Coopman P., Laurent-Matha V., Garcia M., Rochefort H., and Liaudet-Coopman E. A mutated cathepsin-D devoid of its catalytic activity stimulates the growth of cancer cells. Oncogene 20 (2001) 6920-6929
195. Capony F., Rougeot C., Montcourrier P., Cavailles V., Salazar G., and Rochefort H. Increased secretion, altered processing, and glycosylation of pro-cathepsin D in human mammary cancer cells. Cancer Res 49 (1989) 3904-3909
196. Maguchi S., Taniguchi N., and Makita A. Elevated activity and increased mannose-6-phosphate in the carbohydrate moiety of cathepsin D from human hepatoma. Cancer Res 48 (1988) 362-367
197. Mathieu M., Rochefort H., Barenton B., Prebois C., and Vignon F. Interactions of cathepsin-D and insulin-like growth factor-II (IGF-II) on the IGF-II/mannose-6-phosphate receptor in human breast cancer cells and possible consequences on mitogenic activity of IGF-II. Mol Endocrinol 4 (1990) 1327-1335
198. Vignon F., and Rochefort H. Interactions of pro-cathepsin D and IGF-II on the mannose-6-phosphate/IGF-II receptor. Breast Cancer Res Treat 22 (1992) 47-57
199. Vetvicka V., Benes P., and Fusek M. Procathepsin D in breast cancer: what do we know? Effects of ribozymes and other inhibitors. Cancer Gene Ther 9 (2002) 854-863
200. Ohri S.S., Vashishta A., Proctor M., Fusek M., and Vetvicka V. The propeptide of cathepsin D increases proliferation, invasion and metastasis of breast cancer cells. Int J Oncol 32 (2008) 491-498
201. Baldwin E.T., Bhat T.N., Gulnik S., et al. Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design. Proc Natl Acad Sci USA 90 (1993) 6796-6800
202. Metcalf P., and Fusek M. Two crystal structures for cathepsin D: the lysosomal targeting signal and active site. EMBO J 12 (1993) 1293-1302
203. Koelsch G., Metcalf P., Vetvicka V., and Fusek M. Human procathepsin D: three-dimensional model and isolation. Adv Exp Med Biol 362 (1995) 273-278
204. Garcia M., Derocq D., Pujol P., and Rochefort H. Overexpression of transfected cathepsin D in transformed cells increases their malignant phenotype and metastatic potency. Oncogene 5 (1990) 1809-1814
205. Tedone T., Correale M., Barbarossa G., Casavola V., Paradiso A., and Reshkin S.J. Release of the aspartyl protease cathepsin D is associated with and facilitates human breast cancer cell invasion. FASEB J 11 (1997) 785-792
206. Sivaparvathi M., Sawaya R., Chintala S.K., Go Y., Gokaslan Z.L., and Rao J.S. Expression of cathepsin D during the progression of human gliomas. Neurosci Lett 208 (1996) 171-174
207. Lösch A., Schindl M., Kohlberger P., et al. Cathepsin D in ovarian cancer: prognostic value and correlation with p53 expression and microvessel density. Gynecol Oncol 92 (2004) 545-552
208. González-Vela M.C., Garijo M.F., Fernández F., Buelta L., and Val-Bernal J.F. Cathepsin D in host stromal cells is associated with more highly vascular and aggressive invasive breast carcinoma. Histopathology 34 (1999) 35-42
209. Briozzo P., Badet J., Capony F., et al. MCF7 mammary cancer cells respond to bFGF and internalize it following its release from extracellular matrix: a permissive role of cathepsin D. Exp Cell Res 194 (1991) 252-259
210. Piwnica D., Fernandez I., Binart N., Touraine P., Kelly P.A., and Goffin V. A new mechanism for prolactin processing into 16K PRL by secreted cathepsin D. Mol Endocrinol 20 (2006) 3263-3278
211. Benes P., Vashishta A., Saraswat-Ohri S., et al. Effect of procathepsin D activation peptide on gene expression of breast cancer cells. Cancer Lett 239 (2006) 46-54
212. Fusek M., Vetvickova J., and Vetvicka V. Secretion of cytokines in breast cancer cells: the molecular mechanism of procathepsin D proliferative effects. J Interferon Cytokine Res 27 (2007) 191-199
213. Ohri S.S., Vashishta A., Vetvickova J., Fusek M., and Vetvicka V. Procathepsin D expression correlates with invasive and metastatic phenotype of MDA-MB-231 derived cell lines. Int J Biol Macromol 41 (2007) 204-209
214. Vashishta A., Fusek M., and Vetvicka V. Possible role of procathepsin D in human cancer. Folia Microbiol 50 (2005) 71-76
215. Liaudet-Coopman E., Beaujouin M., Derocq D., et al. Cathepsin D: newly discovered functions of a long-standing aspartic protease in cancer and apoptosis. Cancer Lett 237 (2006) 167-179
216. Tumminello F.M., Leto G., Gebbia N., Rausa L., and Bernacki R.J. Evaluation of antitumor and antimetastatic activity of pepstatin A in some experimental tumor models. J Chemother 1 (1989) 1135-1138
217. Tumminello F.M., Bernacki R.J., Gebbia N., and Leto G. Pepstatins: aspartic proteinase inhibitors having potential therapeutic applications. Med Res Rev 13 (1993) 199-208
218. Leto G., Pizzolanti G., Tumminello F.M., and Gebbia N. Effects of E-64 (cysteine-proteinase inhibitor) and pepstatin (aspartyl-proteinase inhibitor) on metastasis formation in mice with mammary and ovarian tumors. In Vivo 8 (1994) 231-236
219. Agostinelli E., and Seiler N. Lysosomotropic compounds and spermine enzymatic oxidation products in cancer therapy (Review). Int J Oncol 31 (2007) 473-484
220. Vetvicka V., and Fusek M. Activation of peripheral blood neutrophils and lymphocytes by human procathepsin D and insulin-like growth factor II. Cell Immunol 156 (1994) 332-341