Cathepsin B and its endogenous inhibitors: the role in tumor malignancy

Cancer and Metastasis Reviews - Tập 9 - Trang 333-352 - 1990
Bonnie F. Sloane1, Kamiar Moin1, Evzen Krepela1, Jurij Rozhin1
1Department of Pharmacology, Wayne State University, Detroit, USA

Tóm tắt

Several lysosomal proteinases including the cysteine proteinase cathepsin B have been implicated in malignant progression of tumors. Many investigators have demonstrated correlations between increased activity of cathepsin B and increased metastatic capability of animal tumors or malignancy of human tumors. Such increases in cathepsin B activity in malignant tumors may reflect alterations in synthesis, in activation and processing, and/or in intracellular trafficking and delivery as well as in the endogenous inhibitors of cathepsin B. Increases in mRNA transcripts for cathepsin B have been observed in both murine and human tumors and multiple transcripts for cathepsin B have been identified, but an association of multiple transcripts with malignancy has not been confirmed. Cathepsin B precursors found in human malignant ascites fluid do not possess mannose-rich carbohydrates suggesting that a defect in the post translational processing of carbohydrate moieties on tumor cathepsin B may be responsible for the release of cathepsin B observed in many tumor systems. However, the intracellular trafficking of cathepsin B responsible for its association with plasma membrane/endosomal systems and for its release willrequire further study as both latent, precursor forms of cathepsin B and native forms of cathepsin B are involved. We speculate that malignant tumor cells adherent to basement membrane are capable of forming a digestive microenvironment in which lysosomal proteinases such as cathepsin B function optimally, a microenvironment similar to that formed between adherent osteoclasts and bone. One of the endogenous cysteine proteinase inhibitors, stefin A, also is affected by malignancy. Reduced expression (mRNA and protein) of stefin A is found as well as a reduction in its inhibitory capacity against cysteine proteinases. The data to date at both the molecular and protein levels supporting a functional role(s) for cathepsin B and its endogenous inhibitors in cancer progression are only correlative. Experimental approaches utilizing well-defined model systems in conjunction with genetic manipulation of cathepsin B and its endogenous inhibitors are needed to provide convincing evidence that cathepsin B has an important role in cancer.

Tài liệu tham khảo

Spyratos F, Maudelonde T, Brouillet JP, Brunet M, Defrenne A, Andrieu C, Hacene K, Desplaces A, Rochefort H: An important marker predicting metastasis in primary breast cancer. Lancet (ii): 1115–1118, 1989 Tandon A, Clark G, Chamness G, Chirgwin J, McGuire WL: Cathepsin D and prognosis in breast cancer. N Engl J Med 322: 297–302, 1990 Pietras RJ, Szego CM: Cathepsin D in breast cancer (Letter to editor). N Engl J Med 322: 1673–1674, 1990 Recklies AD, Poole AR: Proteolytic mechanisms of tissue destruction in tumor growth and metastasis. In: Weiss L, Gilbert HA (eds) Liver metastasis. GK Hall, Boston, 1982, pp 77–95 Sloane BF, Honn KV: Cysteine proteinases and metastasis. Cancer Metastasis Rev 3: 249–263, 1984 Sloane BF, Rozhin J, Hatfield JS, Crissman JD, Honn KV: Plasma membrane-associated cysteine proteinases in human and animal tumors. Exp Cell Biol 55: 209–224, 1987 Recklies AD: Biochemical aspects of cellular migration and invasion. Biorheology 23: 93–103, 1987 Sloane BF: Cathepsin B and cystatins: evidence for a role in cancer progression. Semin Cancer Biol 1: 137–152, 1990 Sloane BF, Krepela E, Lah TT: Regulation of lysosomal proteinases in neoplasia. In: Pretlow TG, Pretlow TP (eds) Aspects of the biochemistry and molecular biology of tumors. Academic Press, NY, in press Collela R, Denhardt D: Anti-cancer activities of naturally occurring cysteine proteinase inhibitors. In: Troll W, Kennedy A (eds) Proteinase inhibitors as cancer chemopreventive agents. Plenum Press, New York, in press. Willstatter R, Bamann E: Uber die proteasen der magenschleimhaut. Erste abhandlung uber die enzyme der leukocyten. Hoppe-Seylers Z Physiol Chem 180: 127–143, 1929 Kornfeld S, Mellman I: The biogenesis of lysosomes. Annu Rev Cell Biol 5: 483–525, 1989 Barrett AJ, Kirschke H: Cathepsin B, cathepsin H, cathepsin L. Meth in Enzymol 80: 535–561, 1981 Chan SJ, San Segundo B, McCormick MB, Steiner DF: Nucleotide and predicted amino acid sequences of cloned human and mouse preprocathepsin B cDNAs. Proc Natl Acad Sci USA 83: 7721–7725, 1986 Hanewinkel H, Glossl J, Kresse H: Biosynthesis of cathepsin B in cultured normal and I-cell fibroblasts. J Biol Chem 262: 12351–12355, 1987 Kominami E, Tsukahara T, Hara K, Katunuma N: Biosyntheses and processing of lysosomal cysteine proteinases in rat macrophages. FEBS Lett 231: 225–228, 1988 Hara K, Kominami E, Katunuma N: Effect of proteinase inhibitors on intracellular processing of cathepsin B, H and L in rat macrophages. FEBS Lett 231: 229–231, 1988 Nishimura Y, Kawabata T, 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: 64–71, 1988 Takahashi T, Dehdarani AH, Yonezawa S, Tang J: Porcine spleen cathepsin B is an exopeptidase. J Biol Chem 261: 9375–9381, 1986 Mason RW: Interaction of lysosomal cysteine proteinases with α2-macroglobulin: conclusive evidence for the endopeptidase activities of cathepsins B and H. Arch Biochem Biophys 273: 367–374, 1989 Rozhin J, Robinson D, Stevens MA, Lah TT, Honn KV, Ryan RE, Sloane BF: Properties of a plasma membraneassociated cathepsin B-like cysteine proteinase in metastatic B16 melanoma variants. Cancer Res 47: 6620–6628, 1987 Kirschke H, Locnikar P, Turk V: Species variations amongst lysosomal cysteine proteinases. FEBS Letts 174: 123–127, 1984 Barrett AJ, Kembhavi AA, Brown MA, Kirschke H, Knight CJ, Tamai M, Hanada K: L-trans-epoxysuccinylleucylamido(4-guanidino)butane (E-64) and its analogues as inhibitors of cysteine proteinases including cathepsins B, H and L. Biochem J 201: 189–198, 1982 Green GDJ, Shaw E: Peptidyl diazomethyl ketones are specific inactivators of thiol proteinases. J Biol Chem 256: 1923–1928, 1981 Crawford C, Mason RW, Wikstrom P, Shaw E: The design of peptidyldiazomethane inhibitors to distinguish between the cysteine proteinases calpain II, cathepsin L and cathepsin B. Biochem J 253: 751–758, 1988 Kirschke H, Shaw E: Rapid inactivation of cathepsin L by Z-Phe-PheCHN2 and Z-Phe-AlaCHN2. Biochem Biophys Res Commun 101: 454–458, 1981 Shaw E: Peptidyl sulfonium salts. J Biol Chem 263: 2768–2772, 1988 Rich DH: Inhibitors of cysteine proteinases. In: Barrett AJ, Salvesen G (eds) Proteinase inhibitors. Elsevier, Amsterdam, 1986, pp 153–178 Demuth HU: Recent developments in inhibiting cysteine and serine proteases. J Enzym Inhib 3: 249–278, 1990 Smith RA, Coles PJ, Spencer RW, Copp LJ, Jones CS, Krantz A: Peptidyl O-acyl hydroxamates: potent new inactivators of cathepsin B. Biochem Biophys Res Commun 155: 1201–1206, 1988 Willenbrock F, Brocklehurst K: A general framework of cysteine-proteinase mechanism deduced from studies on enzymes with structurally different analogous catalytic-site residues Asp-158 and-161 (papain and actinidin), Gly-196 (cathepsin B) and Asn-165 (cathepsin H). Biochem J 227: 521–528, 1985 Lah TT, Buck MR, Honn KV, Crissman JD, Rao NC, Liotta LA, Sloane BF: Degradation of laminin by human tumor cathepsin B. Clin Exp Metastasis 7: 461–468, 1989 Mort JS, Recklies AD: Interrelationship of active and latent secreted human cathepsin B precursors. Biochem J 233: 57–63, 1986 Sloane BF, Dunn JR, Honn KV: Lysosomal cathepsin B: correlation with metastatic potential. Science 212: 1151–1153, 1981 Sloane BF, Honn KV, Sadler JG, Turner WA, Kimpson JJ, Taylor JD: Cathepsin B activity in B16 melanoma cells: a possible marker for metastatic potential. Cancer Res 42: 980–986, 1982 Ryan RE, Crissman JD, Honn KV, Sloane BF: Cathepsin B-like activity in viable tumor cells isolated from rodent tumors. Cancer Res 45: 3636–3641, 1985 Sloane BF, Rozhin J, Johnson K, Taylor H, Crissman JD, Honn KV: Cathepsin B: association with plasma membrane in metastatic tumors. Proc Natl Acad Sci USA 83: 2483–2487, 1986 Sloane BF, Rozhin J, Hatfield JS, Crissman JD, Honn KV: Plasma membrane-associated cysteine proteinases in human and animal tumors. Exp Cell Biol 55: 209–224, 1987 Moin K, Rozhin J, McKernan TB, Sanders VJ, Fong D, Honn KV, Sloane BF: Enhanced levels of cathepsin B mRNA in murine tumors. FEBS Lett 244: 61–64, 1989 Keren Z, LeGrue SJ: Identification of cell surface cathepsin B-like activity on murine melanomas and fibrosarcomas: modulation by butanol extraction. Cancer Res 48: 1416–1421, 1988 Qian F, Bajkowski AS, Steiner DF, Chan SJ, Frankfater A: Expression of five cathepsins in murine melanomas of varving [sic] metastatic potential and normal tissues. Cancer Res 49: 4870–4875, 1989 Recklies AD, Poole AR, Mort JS: A cysteine proteinase secreted from human breast tumors is immunologically related to cathepsin B. Biochem J 207: 633–636, 1982 Mort JS, Leduc M, Recklies A: A latent thiol proteinase from ascitic fluid of patients with neoplasia. Biochim Biophys Acta 662: 173–180, 1981 Lah TT, Clifford JL, Helmer KM, Day NA, Moin K, Honn KV, Crissman JD, Sloane BF: Inhibitory properties of low molecular mass cysteine proteinase inhibitors from human sarcoma. Biochim Biophys Acta 993: 63–73, 1989 Rozhin J, Gomez AP, Ziegler GH, Nelson KK, Chang YS, Fong D, Onoda JM, Honn KV, Sloane BF: Cathepsin B to cysteine proteinase inhibitor balance in metastatic cell subpopulations isolated from murine tumors. Cancer Res, 50: 6278–6284, 1990 Koppel P, Baici A, Keist R, Matzku S, Keller R: Cathepsin B like proteinase as a marker for tumor cell variants. Exp Cell Biol 52: 293–299, 1984 Recklies AD, Tiltman KJ, Stoker TAM, Poole AR: Secretion of proteinases from malignant and non-malignant human breast tissue. Cancer Res 40: 550–556, 1980 Murnane MJ: Cathepsin B expression in human colorectal carcinoma. Cancer Res, in press. Bernhard HP, Darlington, Ruddle FH: Evidence of liver phenotypes in cultured mouse hepatoma cells: synthesis and secretion of serum albumin. Dev Biol 35: 83–96, 1973 San Segundo B, Chan SJ, Steiner DF: Differences in cathepsin B mRNA levels in rat tissue suggest specialized functions. FEBS Lett 201: 251–256, 1986 Fong D, Calhoun DH, Hsieh W-T, Lee B, Wells RD: Isolation of a cDNA clone for the human lysosomal proteinase cathepsin B. Proc Natl Acad Sci USA 83: 2909–2913, 1986 Qian F, Chan SJ, Bajkowski AS, Steiner DF, Frankfater A: Characterization of three cathepsin B mRNA transcripts in murine B16a melanoma. FASEB J 4: A1817, 1990 Azuma T, Pals G, Mohandas TK, Couvreur JM, Taggart RT: Human gastric cathepsin E: predicted sequence, localization to chromosome 1 and sequence homology with other aspartic proteinases. J Biol Chem 264: 16748–16753, 1989 Pagano M, Dalet-Fumeron V, Engler R: The glycosylation state of the precursors of the cathepsin B-like proteinase from human malignant ascitic fluid: Possible implication in the secretory pathway of these proenzymes. Cancer Lett 45: 13–19, 1989 Pagano M, Capony F, Rochefort H: La pro-cathepsine D peut activer in vitro la pro-cathepsine B sécrétée par les cancers ovariens. CR Acad Sci Paris 309: 7–12, 1989 Lowy DR, Willumsen BM: New clue to ras lipid glue. Nature 341: 384–385, 1989 Chi L, Zhu M, Marks N: High affinity binding of rat brain cathepsin B to purified rat/bovine cerebral mannose 6-phosphate receptors. Biol Chem Hoppe-Seyler 371 suppl: 259–264, 1990 vanDongen JM, Willensen R, Ginns EI, Sips HJ, Tager JM, Barranger JA, Reuser AJJ: The subcellular localization of soluble and membrane bound lysosomal enzymes in I-cell fibroblasts: a comparative immunocytochemical study. Eur J Cell Biol 39: 179–189, 1985 Cavanaugh PG, Sloane BF, Bajkowski AS, Gasic GJ, Gasic TB, Honn KV: Involvement of a cathepsin B-like cysteine proteinase in platelet aggregation induced by tumor cells and their shed membrane vesicles. Clin Exp Metastasis 1: 297–307, 1983 Rozhin J, Wade RL, Honn KV, Sloane BF: Membrane-associated cathepsin L: a role in metastasis of melanomas. Biochem Biophys Res Commun 164: 556–561, 1989 Jensen HK, Ledet T: Proteolysis of arterial basement membrane containing different amounts of carbohydrates. Thromb Res 44: 47–53, 1986 Maciewicz RA, Wardale RJ, Etherington DJ, Paraskeva C: Immunodetection of cathepsins B and L present in and secreted from human pre-malignant and malignant colorectal tumour cell lines. Int J Cancer 43: 478–486, 1989 Ohsawa T, Higashi T, Tsuji T: The secretion of high molecular weight cathepsin B from cultured human liver cancers. Acta Med Okayama 43: 9–15, 1989 Goldberg DE, Gabel CA, Kornfeld S: Studies of the biosynthesis of the mannose 6-phosphate receptor in receptor-positive and-deficient cell lines. J Cell Biol 97: 1700–1706, 1983 Mainferme F, Wattiaux R, vonFigura K: Synthesis, transport and processing of cathepsin C in Morris hepatoma 7777 cells and rat hepatocytes. Eur J Biochem 153: 211–216, 1985 Prence EM, Dong J, Sahagian GG. Modulation of the transport of a lysosomal enzyme by PDGF. J Cell Biol 110: 319–326, 1990 Erdel M, Trefz G, Spiess E, Habermaas S, Spring H, Lah T, Ebert W: Localization of cathepsin B in two human lung cancer cell lines. J Histochem Cytochem (in press) Krepela E, Bartek J, Skalkova D: Cytochemical and biochemical evidence of cathepsin B in malignant, transformed and normal breast epithelial cells. J Cell Sci 87: 145–154, 1987 Barrett AJ: The cystatins: a new class of peptidase inhibitors. Trends Biochem Sci 12: 193–196, 1987 Muller-Esterl W, Iwanaga S, Nakanishi S: Kininogens revisited. Trends Biochem Sci 11: 336–339, 1986 Green GDJ, Kembhavi AA, Davies ME, Barrett AJ: Cystatin-like cysteine proteinase inhibitors from human liver. Biochem J 218: 939–946, 1984 Nicklin MJH, Barrett AJ: Inhibition of cysteine proteinases and dipeptidyl peptidase I by egg-white cystatin. Biochem J 223: 245–253, 1984 Hawley-Nelson P, Roop DR, Cheng CK, Krieg TM, Yuspa SH: Molecular cloning of mouse epidermal cystatin A and detection of regulated expression in differentiation and tumorigenesis. Mol Carcinogenesis 1: 202–211, 1988 Rinne A, Jarvinen M, Rasanen O, Hopsu-Havu VK: Acid and neutral cysteine proteinase inhibitor in normal uterine portio and in squamo-epithelial metaplasia, dysplasias and infiltrative carcinoma of the uterine portio. Exp Pathol 26: 67–70, 1984 Kyllonen AP, Jarvinen M, Hopsu-Havu VK, Dorn A, Rasanen O, Larmi T, Rinne A: The behaviour of small molecular cysteine proteinase inhibitors in lung cancers and in surrounding tissue. Acta Histochem 74: 109–113, 1984 Palsdottir A, Abrahamson M, Thorsteinsson L, Arnason A, Olafsson I, Grubb A, Jensson O: A mutation in the cystatin C gene causes hereditary brain hemorrhage. Lancet 1988: 603–604, 1988 Liotta LA, Stetler-Stevenson WG: Metalloproteinases and cancer invasion. Semin Cancer Biol 1: 99–106, 1990 Redhead S: Osteoclastic bone resorption: all hands to the proton pump. J NIH Res 2: 57–60, 1990 Baron R: Molecular mechanism of bone resorption by osteoclasts. Anat Rec 224: 317–324, 1989 Canalis E, McCarthy T, Centrella M: Growth factors and the regulation of bone remodeling. J Clin Invest 81: 277–281, 1988 Kornfeld S: Lysosomal enzyme targeting. Biochem Soc Trans 18: 367–374, 1990 Kornfeld S: Trafficking of lysosomal enzymes. FASEB J 1: 462–468, 1987 Roederer M, Bowser R, Murphy RF: Kinetics and temperature dependence of exposure of endocytosed material to proteolytic enzymes and low pH: evidence for a maturation model for the formation of lysosomes. J Cell Physiol 131: 200–209, 1987 Roederer M, Barry JR, Wilson RB, Murphy RF: Endosomes can undergo an ATP-dependent density increase in the absence of dense lysosomes. Eur J Cell Biol 51: 229–234, 1990 Silver IA, Murrills RJ, Etherington DJ: Microelectrode studies on the acid microenvironment beneath adherent macrophages and osteoclasts. Exp Cell Res 175: 266–276, 1988 Grossi IM, Hatfield JS, Fitzgerald LA, Newcombe M, Taylor JD, Honn KV: Role of tumor cell glycoproteins immunologically related to glycoproteins Ib and IIb/IIIa in tumor cell-platelet and tumor cell-matrix interactions. FASEB J 2: 2385–2395, 1988 Ghelsen KR, Argraves WS, Pierschbacher MD, Ruoslahti E: Inhibition of in vitro tumor cell invasion by Arg-Gly-Asp-containing synthetic peptides. J Cell Biol 106: 925–930, 1988 Kramer RH, McDonald KA, Crowley E, Ramos DM, Damsky CH: Melanoma cell adhesion to basement membrane mediated by integrin-related complexes. Cancer Res 49: 393–402, 1989 Skudlarek MD, Swank RT: Turnover of two lysosomal enzymes in macrophages. J Biol Chem 256: 10137–10144, 1981 Reilly JJ, Mason RW, Chen P, Joseph LJ, Sukhatme VP, Yee R, Chapman HA: Synthesis and processing of cathepsin L, an elastase, by human alveolar macrophages. Biochem J 257: 493–498, 1989 Sloane BF, Ryan RE, Rozhin J, Lah TT, Crissman JD, Honn KV: Cathepsin B: A proteinase linked to metastasis? In: Tschesch H (ed) Proteinases in inflammation and tumor invasion. deGruyter, Berlin, 1986, pp 93–106 Achkar C, Gong Q, Frankfater A, Bajkowski AS: Differences in targeting and secretion of cathepsins B and L by BALB/3T3 fibroblasts and Molony murine sarcoma virus transformed BALB/3T3 fibroblasts. J Biol Chem 265: 13650–13654, 1990 Dong J, Prence EM, Sahagian GG: Mechanism for selective secretion of a lysosomal proteinase by transformed mouse fibroblasts. J Biol Chem 264: 7377–7383, 1989 Dong J, Sahagian GG: Basis for low affinity binding of a lysosomal cysteine protease to the cation-independent mannose 6-phosphate receptor. J Biol Chem 265: 4210–4217, 1990 Heuser J: Changes in lysosomal shape and distribution correlated with changes in cytoplasmic pH. J Cell Biol 108: 855–864, 1989 Krepela E, Vesely P, Chaloupkova A, Zicha D, Urbanec P, Rasnick D, Vicar J: Cathepsin B in cells of two rat sarcomas with different rates of spontaneous metastasis. Neoplasma 36: 529–540, 1989 Murphy RF: Processing of endocytosed material. Advan Cell Biol 2: 159–180, 1988 Baricos WH, Zhou Y, Mason RW, Barrett AJ: Human kidney cathepsins B and L. Biochem J 252: 301–304, 1988 Gingras MC, Jarolim L, Finch J, Bowden GT, Wright JA, Greenberg AH: Transient alterations in the expression of protease and extracellular matrix genes during metastatic lung colonization by H-ras-transformed 10T1/2 fibroblasts. Cancer Res 50: 4061–4066, 1990