Abstract
The role of proteases in cancer was originally thought to be limited to the breakdown of basement membranes and extracellular matrix (ECM), thereby promoting cancer cell invasion into surrounding normal tissues. It is now well understood that proteases play a much more complicated role in all stages of cancer progression and that not only tumor cells, but also stromal cells are an important source of proteases in the tumor microenvironment. Among all the proteolytic enzymes potentially associated with cancer, some proteases have taken on heightened importance due to their significant up-regulation and ability to participate at multiple stages of cancer progression and metastasis. In this review, we discuss some of the advances in understanding of the roles of several key proteases from different classes in the development and progression of cancer and the potential to leverage their upregulated activity for the development of novel targeted treatment strategies.
Acknowledgments
The authors gratefully acknowledge W. Michael Kavanaugh for the critical review of the manuscript. Probody™ is a trademark of CytomX Therapeutics, Inc.
References
Akkari, L., Gocheva, V., Quick, M.L., Kester, J.C., Spencer, A.K., Garfall, A.L., Bowman, R.L., and Joyce, J.A. (2016). Combined deletion of cathepsin protease family members reveals compensatory mechanisms in cancer. Genes Dev. 30, 220–232.10.1101/gad.270439.115Suche in Google Scholar PubMed PubMed Central
Albright, C.F., Graciani, N., Han, W., Yue, E., Stein, R., Lai, Z., Diamond, M., Dowling, R., Grimminger, L., Zhang, S.Y., et al. (2005). Matrix metalloproteinase-activated doxorubicin prodrugs inhibit HT1080 xenograft growth better than doxorubicin with less toxicity. Mol. Cancer Ther. 4, 751–760.10.1158/1535-7163.MCT-05-0006Suche in Google Scholar PubMed
Ardi, V.C., Kupriyanova, T.A., Deryugina, E.I., and Quigley, J.P. (2007). Human neutrophils uniquely release TIMP-free MMP-9 to provide a potent catalytic stimulator of angiogenesis. Proc. Natl. Acad. Sci. USA 104, 20262–20267.10.1073/pnas.0706438104Suche in Google Scholar PubMed PubMed Central
Bajjuri, K.M., Liu, Y., Liu, C., and Sinha, S.C. (2011). The legumain protease-activated auristatin prodrugs suppress tumor growth and metastasis without toxicity. ChemMedChem 6, 54–59.10.1002/cmdc.201000478Suche in Google Scholar PubMed PubMed Central
Barrett, A.J. (1992). Cellular proteolysis. An overview. Ann. N Y Acad. Sci. 674, 1–15.10.1111/j.1749-6632.1992.tb27472.xSuche in Google Scholar PubMed
Barthel, B.L., Rudnicki, D.L., Kirby, T.P., Colvin, S.M., Burkhart, D.J., and Koch, T.H. (2012). Synthesis and biological characterization of protease-activated prodrugs of doxazolidine. J. Med. Chem. 55, 6595–6607.10.1021/jm300714pSuche in Google Scholar PubMed PubMed Central
Baurain, R., Masquelier, M., Deprez-De Campeneere, D., and Trouet, A. (1980). Amino acid and dipeptide derivatives of daunorubicin. 2. Cellular pharmacology and antitumor activity on L1210 leukemic cells in vitro and in vivo. J. Med. Chem. 23, 1171–1174.10.1021/jm00185a004Suche in Google Scholar PubMed
Ben-Nun, Y., Merquiol, E., Brandis, A., Turk, B., Scherz, A., and Blum, G. (2015). Photodynamic quenched cathepsin activity based probes for cancer detection and macrophage targeted therapy. Theranostics 5, 847–862.10.7150/thno.10854Suche in Google Scholar PubMed PubMed Central
Ben-Nun, Y., Fichman, G., Adler-Abramovich, L., Turk, B., Gazit, E., and Blum, G. (2017). Cathepsin nanofiber substrates as potential agents for targeted drug delivery. J. Control Release 257, 60–67.10.1016/j.jconrel.2016.11.028Suche in Google Scholar PubMed
Berndt, S., Bruyère, F., Jost, M., and Noël, A. (2008). In Vitro and In Vivo Models of Angiogenesis to Dissect MMP Functions (New York, USA: Springer).10.1007/978-0-387-69057-5_16Suche in Google Scholar
Bhatt, A.S., Takeuchi, T., Ylstra, B., Ginzinger, D., Albertson, D., Shuman, M.A., and Craik, C.S. (2003). Quantitation of membrane type serine protease 1 (MT-SP1) in transformed and normal cells. Biol. Chem. 384, 257–266.10.1515/BC.2003.029Suche in Google Scholar
Blasi, F. and Carmeliet, P. (2002). uPAR: a versatile signalling orchestrator. Nat. Rev. Mol. Cell Biol. 3, 932–943.10.1038/nrm977Suche in Google Scholar
Bocheva, G., Rattenholl, A., Kempkes, C., Goerge, T., Lin, C.Y., D’Andrea, M.R., Stander, S., and Steinhoff, M. (2009). Role of matriptase and proteinase-activated receptor-2 in nonmelanoma skin cancer. J. Invest. Dermatol. 129, 1816–1823.10.1038/jid.2008.449Suche in Google Scholar
Boonstra, M.C., van Driel, P.B., van Willigen, D.M., Stammes, M.A., Prevoo, H.A., Tummers, Q.R., Mazar, A.P., Beekman, F.J., Kuppen, P.J., van de Velde, C.J., et al. (2015). uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery. Oncotarget 6, 14260–14273.10.18632/oncotarget.3680Suche in Google Scholar
Boustany, L.M., Wong, L., White, C.W., Diep, L., Huang, Y., Liu, S., Richardson, J.H., Kavanaugh, W.M., and Irving, B.A. (2018). Abstract A164: EGFR-CD3 bispecific Probody™ therapeutic induces tumor regressions and increases maximum tolerated dose >60-fold in preclinical studies. Mol. Cancer Ther. 17, A164.10.1158/1535-7163.TARG-17-A164Suche in Google Scholar
Campo, E., Munoz, J., Miquel, R., Palacin, A., Cardesa, A., Sloane, B.F., and Emmert-Buck, M.R. (1994). Cathepsin B expression in colorectal carcinomas correlates with tumor progression and shortened patient survival. Am. J. Pathol. 145, 301–309.Suche in Google Scholar
Cavallo-Medved, D., Dosescu, J., Linebaugh, B.E., Sameni, M., Rudy, D., and Sloane, B.F. (2003). Mutant K-ras regulates cathepsin B localization on the surface of human colorectal carcinoma cells. Neoplasia 5, 507–519.10.1016/S1476-5586(03)80035-0Suche in Google Scholar
Chakravarty, P.K., Carl, P.L., Weber, M.J., and Katzenellenbogen, J.A. (1983). Plasmin-activated prodrugs for cancer chemotherapy. 1. Synthesis and biological activity of peptidylacivicin and peptidylphenylenediamine mustard. J. Med. Chem. 26, 633–638.10.1021/jm00359a003Suche in Google Scholar PubMed
Chau, Y., Tan, F.E., and Langer, R. (2004). Synthesis and characterization of dextran−peptide−methotrexate conjugates for tumor targeting via mediation by matrix metalloproteinase II and matrix metalloproteinase IX. Bioconjug. Chem. 15, 931–941.10.1021/bc0499174Suche in Google Scholar PubMed
Chen, J.M., Dando, P.M., Rawlings, N.D., Brown, M.A., Young, N.E., Stevens, R.A., Hewitt, E., Watts, C., and Barrett, A.J. (1997). Cloning, isolation, and characterization of mammalian legumain, an asparaginyl endopeptidase. J. Biol. Chem. 272, 8090–8098.10.1074/jbc.272.12.8090Suche in Google Scholar PubMed
Chipman, S.D., Oldham, F.B., Pezzoni, G., and Singer, J.W. (2006). Biological and clinical characterization of paclitaxel poliglumex (PPX, CT-2103), a macromolecular polymer-drug conjugate. Int. J. Nanomed. 1, 375–383.10.2147/nano.2006.1.4.375Suche in Google Scholar PubMed PubMed Central
Choi, K.Y., Swierczewska, M., Lee, S., and Chen, X. (2012). Protease-activated drug development. Theranostics 2, 156–178.10.7150/thno.4068Suche in Google Scholar
Coussens, L.M., Fingleton, B., and Matrisian, L.M. (2002). Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295, 2387–2392.10.1126/science.1067100Suche in Google Scholar
Creemers, L.B., Hoeben, K.A., Jansen, D.C., Buttle, D.J., Beertsen, W., and Everts, V. (1998). Participation of intracellular cysteine proteinases, in particular cathepsin B, in degradation of collagen in periosteal tissue explants. Matrix Biol. 16, 575–584.10.1016/S0945-053X(98)90068-3Suche in Google Scholar
Crowley, C.W., Cohen, R.L., Lucas, B.K., Liu, G., Shuman, M.A., and Levinson, A.D. (1993). Prevention of metastasis by inhibition of the urokinase receptor. Proc. Natl. Acad. Sci. USA 90, 5021–5025.10.1073/pnas.90.11.5021Suche in Google Scholar PubMed PubMed Central
Darragh, M.R., Schneider, E.L., Lou, J., Phojanakong, P.J., Farady, C.J., Marks, J.D., Hann, B.C., and Craik, C.S. (2010). Tumor detection by imaging proteolytic activity. Cancer Res. 70, 1505–1512.10.1158/0008-5472.CAN-09-1640Suche in Google Scholar PubMed PubMed Central
Decock, J., Thirkettle, S., Wagstaff, L., and Edwards, D.R. (2011). Matrix metalloproteinases: protective roles in cancer. J. Cell Mol. Med. 15, 1254–1265.10.1111/j.1582-4934.2011.01302.xSuche in Google Scholar PubMed PubMed Central
Desnoyers, L.R., Vasiljeva, O., Richardson, J.H., Yang, A., Menendez, E.E., Liang, T.W., Wong, C., Bessette, P.H., Kamath, K., Moore, S.J., et al. (2013). Tumor-specific activation of an EGFR-targeting probody enhances therapeutic index. Sci. Transl. Med. 5, 207ra144.10.1126/scitranslmed.3006682Suche in Google Scholar PubMed
Deussing, J., Kouadio, M., Rehman, S., Werber, I., Schwinde, A., and Peters, C. (2002). Identification and characterization of a dense cluster of placenta-specific cysteine peptidase genes and related genes on mouse chromosome 13. Genomics 79, 225–240.10.1006/geno.2002.6696Suche in Google Scholar PubMed
Dudani, J.S., Warren, A.D., and Bhatia, S.N. (2018). Harnessing protease activity to improve cancer care. Annu. Rev. Cancer Biol. 2, 353–376.10.1146/annurev-cancerbio-030617-050549Suche in Google Scholar
Duffy, M.J., Duggan, C., Mulcahy, H.E., McDermott, E.W., and O’Higgins, N.J. (1998). Urokinase plasminogen activator: a prognostic marker in breast cancer including patients with axillary node-negative disease. Clin. Chem. 44, 1177–1183.10.1093/clinchem/44.6.1177Suche in Google Scholar
Duffy, M.J., McGowan, P.M., Harbeck, N., Thomssen, C., and Schmitt, M. (2014). uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studies. Breast Cancer Res. 16, 428.10.1186/s13058-014-0428-4Suche in Google Scholar
Duriseti, S., Goetz, D.H., Hostetter, D.R., LeBeau, A.M., Wei, Y., and Craik, C.S. (2010). Antagonistic anti-urokinase plasminogen activator receptor (uPAR) antibodies significantly inhibit uPAR-mediated cellular signaling and migration. J. Biol. Chem. 285, 26878–26888.10.1074/jbc.M109.077677Suche in Google Scholar
Egeblad, M. and Werb, Z. (2002). New functions for the matrix metalloproteinases in cancer progression. Nat. Rev. Cancer 2, 161–174.10.1038/nrc745Suche in Google Scholar
Ertongur, S., Lang, S., Mack, B., Wosikowski, K., Muehlenweg, B., and Gires, O. (2004). Inhibition of the invasion capacity of carcinoma cells by WX-UK1, a novel synthetic inhibitor of the urokinase-type plasminogen activator system. Int. J. Cancer 110, 815–824.10.1002/ijc.20192Suche in Google Scholar
Fernandez, P.L., Farre, X., Nadal, A., Fernandez, E., Peiro, N., Sloane, B.F., Shi, G.P., Chapman, H.A., Campo, E., and Cardesa, A. (2001). Expression of cathepsins B and S in the progression of prostate carcinoma. Int. J. Cancer 95, 51–55.10.1002/1097-0215(20010120)95:1<51::AID-IJC1009>3.0.CO;2-JSuche in Google Scholar
Folgueras, A.R., Pendas, A.M., Sanchez, L.M., and Lopez-Otin, C. (2004). Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies. Int. J. Dev. Biol. 48, 411–424.10.1387/ijdb.041811afSuche in Google Scholar
Forbs, D., Thiel, S., Stella, M.C., Sturzebecher, A., Schweinitz, A., Steinmetzer, T., Sturzebecher, J., and Uhland, K. (2005). In vitro inhibition of matriptase prevents invasive growth of cell lines of prostate and colon carcinoma. Int. J. Oncol. 27, 1061–1070.10.3892/ijo.27.4.1061Suche in Google Scholar
Freije, J.M., Balbin, M., Pendas, A.M., Sanchez, L.M., Puente, X.S., and Lopez-Otin, C. (2003). Matrix metalloproteinases and tumor progression. Adv. Exp. Med. Biol. 532, 91–107.10.1007/978-1-4615-0081-0_9Suche in Google Scholar
Frosch, B.A., Berquin, I., Emmert-Buck, M.R., Moin, K., and Sloane, B.F. (1999). Molecular regulation, membrane association and secretion of tumor cathepsin B. APMIS 107, 28–37.10.1111/j.1699-0463.1999.tb01523.xSuche in Google Scholar
Gabrijelcic, D., Svetic, B., Spaic, D., Skrk, J., Budihna, M., Dolenc, I., Popovic, T., Cotic, V., and Turk, V. (1992). Cathepsins B, H and L in human breast carcinoma. Eur. J. Clin. Chem. Clin. Biochem. 30, 69–74.Suche in Google Scholar
Gawenda, J., Traub, F., Luck, H.J., Kreipe, H., and von Wasielewski, R. (2007). Legumain expression as a prognostic factor in breast cancer patients. Breast Cancer Res. Treat. 102, 1–6.10.1007/s10549-006-9311-zSuche in Google Scholar
Gebleux, R., Stringhini, M., Casanova, R., Soltermann, A., and Neri, D. (2017). Non-internalizing antibody-drug conjugates display potent anti-cancer activity upon proteolytic release of monomethyl auristatin E in the subendothelial extracellular matrix. Int. J. Cancer 140, 1670–1679.10.1002/ijc.30569Suche in Google Scholar PubMed PubMed Central
Gerspach, J., Nemeth, J., Munkel, S., Wajant, H., and Pfizenmaier, K. (2006). Target-selective activation of a TNF prodrug by urokinase-type plasminogen activator (uPA) mediated proteolytic processing at the cell surface. Cancer Immunol. Immunother. 55, 1590–1600.10.1007/s00262-006-0162-6Suche in Google Scholar PubMed
Gocheva, V. and Joyce, J.A. (2007). Cysteine cathepsins and the cutting edge of cancer invasion. Cell Cycle 6, 60–64.10.4161/cc.6.1.3669Suche in Google Scholar PubMed
Gocheva, V., Wang, H.W., Gadea, B.B., Shree, T., Hunter, K.E., Garfall, A.L., Berman, T., and Joyce, J.A. (2010). IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev. 24, 241–255.10.1158/1538-7445.AM10-LB-379Suche in Google Scholar
Gu, G., Xia, H., Hu, Q., Liu, Z., Jiang, M., Kang, T., Miao, D., Tu, Y., Pang, Z., Song, Q., et al. (2013). PEG-co-PCL nanoparticles modified with MMP-2/9 activatable low molecular weight protamine for enhanced targeted glioblastoma therapy. Biomaterials 34, 196–208.10.1016/j.biomaterials.2012.09.044Suche in Google Scholar PubMed
Harbeck, N., Kates, R.E., Schmitt, M., Gauger, K., Kiechle, M., Janicke, F., Thomassen, C., Look, M.P., and Foekens, J.A. (2004). Urokinase-type plasminogen activator and its inhibitor type 1 predict disease outcome and therapy response in primary breast cancer. Clin. Breast Cancer 5, 348–352.10.3816/CBC.2004.n.040Suche in Google Scholar
Heidtmann, H.H., Salge, U., Abrahamson, M., Bencina, M., Kastelic, L., Kopitar-Jerala, N., Turk, V., and Lah, T.T. (1997). Cathepsin B and cysteine proteinase inhibitors in human lung cancer cell lines. Clin. Exp. Metastasis 15, 368–381.10.1023/A:1018494020001Suche in Google Scholar
Herszenyi, L., Farinati, F., Cardin, R., Istvan, G., Molnar, L.D., Hritz, I., De Paoli, M., Plebani, M., and Tulassay, Z. (2008). Tumor marker utility and prognostic relevance of cathepsin B, cathepsin L, urokinase-type plasminogen activator, plasminogen activator inhibitor type-1, CEA and CA 19-9 in colorectal cancer. BMC Cancer 8, 194.10.1186/1471-2407-8-194Suche in Google Scholar PubMed PubMed Central
Hirano, T. and Takeuchi, S. (1994). Serum cathepsin-B levels and urinary-excretion of cathepsin-B in the patients with colorectal-cancer – possible indicators for tumor malignancy. Int. J. Oncol. 4, 151–153.10.3892/ijo.4.1.151Suche in Google Scholar PubMed
Hojilla, C.V., Mohammed, F.F., and Khokha, R. (2003). Matrix metalloproteinases and their tissue inhibitors direct cell fate during cancer development. Br. J. Cancer 89, 1817–1821.10.1038/sj.bjc.6601327Suche in Google Scholar PubMed PubMed Central
Janicke, F., Prechtl, A., Thomssen, C., Harbeck, N., Meisner, C., Untch, M., Sweep, C.G., Selbmann, H.K., Graeff, H., Schmitt, M., et al. (2001). Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1. J. Natl. Cancer Inst. 93, 913–920.10.1093/jnci/93.12.913Suche in Google Scholar
Jeong, Y., Lee, K.H., Park, H., and Choi, J. (2015). Enhanced detection of single-cell-secreted proteins using a fluorescent immunoassay on the protein-G-terminated glass substrate. Int. J. Nanomed. 10, 7197–7205.10.2147/IJN.S92596Suche in Google Scholar
Katz, J., Janik, J.E., and Younes, A. (2011). Brentuximab Vedotin (SGN-35). Clin. Cancer Res. 17, 6428–6436.10.1158/1078-0432.CCR-11-0488Suche in Google Scholar
Kessenbrock, K., Plaks, V., and Werb, Z. (2010). Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141, 52–67.10.1016/j.cell.2010.03.015Suche in Google Scholar
Khan, A., Krishna, M., Baker, S.P., and Banner, B.F. (1998). Cathepsin B and tumor-associated laminin expression in the progression of colorectal adenoma to carcinoma. Mod. Pathol. 11, 704–708.Suche in Google Scholar
Killeen, S.D., Andrews, E.J., Wang, J.H., Wu, T., Schmalix, W., Muehlenweg, B., and Redmond, H.P. (2007). Inhibition of urokinase plasminogen activator with a novel enzyme inhibitor, WXC-340, ameliorates endotoxin and surgery-accelerated growth of murine metastases. Br. J. Cancer 96, 262–268.10.1038/sj.bjc.6603550Suche in Google Scholar
Kobayashi, H., Schmitt, M., Goretzki, L., Chucholowski, N., Calvete, J., Kramer, M., Gunzler, W.A., Janicke, F., and Graeff, H. (1991). Cathepsin B efficiently activates the soluble and the tumor cell receptor-bound form of the proenzyme urokinase-type plasminogen activator (Pro-uPA). J. Biol. Chem. 266, 5147–5152.10.1016/S0021-9258(19)67767-7Suche in Google Scholar
Kobayashi, H., Moniwa, N., Sugimura, M., Shinohara, H., Ohi, H., and Terao, T. (1993). Effects of membrane-associated cathepsin B on the activation of receptor-bound prourokinase and subsequent invasion of reconstituted basement membranes. Biochim. Biophys. Acta 1178, 55–62.10.1016/0167-4889(93)90109-3Suche in Google Scholar
Koblinski, J.E., Dosescu, J., Sameni, M., Moin, K., Clark, K., and Sloane, B.F. (2002). Interaction of human breast fibroblasts with collagen I increases secretion of procathepsin B. J. Biol. Chem. 277, 32220–32227.10.1074/jbc.M204708200Suche in Google Scholar PubMed
Kondo, M., Asai, T., Katanasaka, Y., Sadzuka, Y., Tsukada, H., Ogino, K., Taki, T., Baba, K., and Oku, N. (2004). Anti-neovascular therapy by liposomal drug targeted to membrane type-1 matrix metalloproteinase. Int. J. Cancer 108, 301–306.10.1002/ijc.11526Suche in Google Scholar PubMed
Kos, J., Smid, A., Krasovec, M., Svetic, B., Lenarcic, B., Vrhovec, I., Skrk, J., and Turk, V. (1995). Lysosomal proteases cathepsins D, B, H, L and their inhibitors stefins A and B in head and neck cancer. Biol. Chem. Hoppe-Seyler 376, 401–405.10.1515/bchm3.1995.376.7.401Suche in Google Scholar PubMed
Kos, J., Stabuc, B., Schweiger, A., Krasovec, M., Cimerman, N., Kopitar-Jerala, N., and 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.Suche in Google Scholar
Kos, J., Nielsen, H.J., Krasovec, M., Christensen, I.J., Cimerman, N., Stephens, R.W., and Brunner, N. (1998). Prognostic values of cathepsin B and carcinoembryonic antigen in sera of patients with colorectal cancer. Clin. Cancer Res. 4, 1511–1516.Suche in Google Scholar
Kramer, L., Renko, M., Zavrsnik, J., Turk, D., Seeger, M.A., Vasiljeva, O., Grutter, M.G., Turk, V., and Turk, B. (2017a). Non-invasive in vivo imaging of tumour-associated cathepsin B by a highly selective inhibitory DARPin. Theranostics 7, 2806–2821.10.7150/thno.19081Suche in Google Scholar PubMed PubMed Central
Kramer, L., Turk, D., and Turk, B. (2017b). The future of cysteine cathepsins in disease management. Trends Pharmacol. Sci. 38, 873–898.10.1016/j.tips.2017.06.003Suche in Google Scholar PubMed
Kwon, E.J., Dudani, J.S., and Bhatia, S.N. (2017). Ultrasensitive tumour-penetrating nanosensors of protease activity. Nat Biomed Eng 1, 0054.10.1038/s41551-017-0054Suche in Google Scholar PubMed PubMed Central
Lah, T.T., Cercek, M., Blejec, A., Kos, J., Gorodetsky, E., Somers, R., and Daskal, I. (2000). Cathepsin B, a prognostic indicator in lymph node-negative breast carcinoma patients: comparison with cathepsin D, cathepsin L, and other clinical indicators. Clin. Cancer Res. 6, 578–584.Suche in Google Scholar
LeBeau, A.M., Duriseti, S., Murphy, S.T., Pepin, F., Hann, B., Gray, J.W., VanBrocklin, H.F., and Craik, C.S. (2013a). Targeting uPAR with antagonistic recombinant human antibodies in aggressive breast cancer. Cancer Res. 73, 2070–2081.10.1158/0008-5472.CAN-12-3526Suche in Google Scholar PubMed PubMed Central
LeBeau, A.M., Lee, M., Murphy, S.T., Hann, B.C., Warren, R.S., Delos Santos, R., Kurhanewicz, J., Hanash, S.M., VanBrocklin, H.F., and Craik, C.S. (2013b). Imaging a functional tumorigenic biomarker in the transformed epithelium. Proc. Natl. Acad. Sci. USA 110, 93–98.10.1073/pnas.1218694110Suche in Google Scholar PubMed PubMed Central
LeBeau, A.M., Sevillano, N., King, M.L., Duriseti, S., Murphy, S.T., Craik, C.S., Murphy, L.L., and VanBrocklin, H.F. (2014). Imaging the urokinase plasminongen activator receptor in preclinical breast cancer models of acquired drug resistance. Theranostics 4, 267–279.10.7150/thno.7323Suche in Google Scholar PubMed PubMed Central
LeBeau, A.M., Sevillano, N., Markham, K., Winter, M.B., Murphy, S.T., Hostetter, D.R., West, J., Lowman, H., Craik, C.S., and VanBrocklin, H.F. (2015). Imaging active urokinase plasminogen activator in prostate cancer. Cancer Res. 75, 1225–1235.10.1158/0008-5472.CAN-14-2185Suche in Google Scholar PubMed PubMed Central
Leto, G., Tumminello, F.M., Pizzolanti, G., Montalto, G., Soresi, M., and Gebbia, N. (1997). Lysosomal cathepsins B and L and Stefin A blood levels in patients with hepatocellular carcinoma and/or liver cirrhosis: potential clinical implications. Oncology 54, 79–83.10.1159/000227666Suche in Google Scholar PubMed
Li, C., Yu, D.-F., Newman, R.A., Cabral, F., Stephens, L.C., Hunter, N., Milas, L., and Wallace, S. (1998). Complete regression of well-established tumors using a novel water-soluble poly(L-glutamic acid)-paclitaxel conjugate. Cancer Res. 58, 2404–2409.Suche in Google Scholar
Lin, J. and Sagert, J. (2018). Targeting Drug Conjugates to the Tumor Microenvironment: Probody Drug Conjugates (Cham, Switzerland: Humana Press).10.1007/978-3-319-78154-9_12Suche in Google Scholar
Linebaugh, B.E., Sameni, M., Day, N.A., Sloane, B.F., and Keppler, D. (1999). Exocytosis of active cathepsin B enzyme activity at pH 7.0, inhibition and molecular mass. Eur. J. Biochem. 264, 100–109.10.1046/j.1432-1327.1999.00582.xSuche in Google Scholar PubMed
Liotta, L.A. and Kohn, E.C. (2001). The microenvironment of the tumour-host interface. Nature 411, 375–379.10.1038/35077241Suche in Google Scholar PubMed
List, K., Haudenschild, C.C., Szabo, R., Chen, W., Wahl, S.M., Swaim, W., Engelholm, L.H., Behrendt, N., and Bugge, T.H. (2002). Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis. Oncogene 21, 3765–3779.10.1038/sj.onc.1205502Suche in Google Scholar PubMed
List, K., Szabo, R., Wertz, P.W., Segre, J., Haudenschild, C.C., Kim, S.Y., and Bugge, T.H. (2003). Loss of proteolytically processed filaggrin caused by epidermal deletion of Matriptase/MT-SP1. J. Cell Biol. 163, 901–910.10.1083/jcb.200304161Suche in Google Scholar PubMed PubMed Central
List, K., Szabo, R., Molinolo, A., Sriuranpong, V., Redeye, V., Murdock, T., Burke, B., Nielsen, B.S., Gutkind, J.S., and Bugge, T.H. (2005). Deregulated matriptase causes ras-independent multistage carcinogenesis and promotes ras-mediated malignant transformation. Genes Dev. 19, 1934–1950.10.1101/gad.1300705Suche in Google Scholar PubMed PubMed Central
List, K., Bugge, T.H., and Szabo, R. (2006a). Matriptase: potent proteolysis on the cell surface. Mol Med 12, 1–7.10.2119/2006-00022.ListSuche in Google Scholar PubMed PubMed Central
List, K., Szabo, R., Molinolo, A., Nielsen, B.S., and Bugge, T.H. (2006b). Delineation of matriptase protein expression by enzymatic gene trapping suggests diverging roles in barrier function, hair formation, and squamous cell carcinogenesis. Am. J. Pathol. 168, 1513–1525.10.2353/ajpath.2006.051071Suche in Google Scholar PubMed PubMed Central
Liu, C., Sun, C., Huang, H., Janda, K., and Edgington, T. (2003a). Overexpression of legumain in tumors is significant for invasion/metastasis and a candidate enzymatic target for prodrug therapy. Cancer Res. 63, 2957–2964.Suche in Google Scholar
Liu, S., Aaronson, H., Mitola, D.J., Leppla, S.H., and Bugge, T.H. (2003b). Potent antitumor activity of a urokinase-activated engineered anthrax toxin. Proc. Natl. Acad. Sci. USA 100, 657–662.10.1073/pnas.0236849100Suche in Google Scholar PubMed PubMed Central
Liu, S., Redeye, V., Kuremsky, J.G., Kuhnen, M., Molinolo, A., Bugge, T.H., and Leppla, S.H. (2005). Intermolecular complementation achieves high-specificity tumor targeting by anthrax toxin. Nat. Biotechnol. 23, 725-730.10.1038/nbt1091Suche in Google Scholar PubMed PubMed Central
Loadman, P.M., Bibby, M.C., Double, J.A., Al-Shakhaa, W.M., and Duncan, R. (1999). Pharmacokinetics of PK1 and doxorubicin in experimental colon tumor models with differing responses to PK1. Clin. Cancer Res. 5, 3682–3688.Suche in Google Scholar
Look, M.P., van Putten, W.L., Duffy, M.J., Harbeck, N., Christensen, I.J., Thomssen, C., Kates, R., Spyratos, F., Ferno, M., Eppenberger-Castori, S., et al. (2002). Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients. J. Natl. Cancer Inst. 94, 116–128.10.1093/jnci/94.2.116Suche in Google Scholar PubMed
Luo, Y., Zhou, H., Krueger, J., Kaplan, C., Lee, S.H., Dolman, C., Markowitz, D., Wu, W., Liu, C., Reisfeld, R.A., et al. (2006). Targeting tumor-associated macrophages as a novel strategy against breast cancer. J. Clin. Invest. 116, 2132–2141.10.1172/JCI27648Suche in Google Scholar PubMed PubMed Central
Luthgens, K., Ebert, W., Trefz, G., Gabrijelcic, D., Turk, V., and Lah, T. (1993). Cathepsin B and cysteine proteinase inhibitors in bronchoalveolar lavage fluid of lung cancer patients. Cancer Detect. Prev. 17, 387–397.Suche in Google Scholar
Lutolf, M.P., Lauer-Fields, J.L., Schmoekel, H.G., Metters, A.T., Weber, F.E., Fields, G.B., and Hubbell, J.A. (2003). Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: engineering cell-invasion characteristics. Proc. Natl. Acad. Sci. USA 100, 5413–5418.10.1073/pnas.0737381100Suche in Google Scholar PubMed PubMed Central
Maciewicz, R.A., Wardale, R.J., Etherington, D.J., and Paraskeva, C. (1989). Immunodetection of cathepsins B and L present in and secreted from human pre-malignant and malignant colorectal tumour cell lines. Int. J. Cancer 43, 478–486.10.1002/ijc.2910430323Suche in Google Scholar PubMed
Mahmood, N., Mihalcioiu, C., and Rabbani, S.A. (2018). Multifaceted role of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR): diagnostic, prognostic, and therapeutic applications. Front. Oncol. 8, 24.10.3389/fonc.2018.00024Suche in Google Scholar PubMed PubMed Central
Mai, J., Sameni, M., Mikkelsen, T., and Sloane, B.F. (2002). Degradation of extracellular matrix protein tenascin-C by cathepsin B: an interaction involved in the progression of gliomas. Biol. Chem. 383, 1407–1413.10.1515/BC.2002.159Suche in Google Scholar PubMed
Manoury, B., Hewitt, E.W., Morrice, N., Dando, P.M., Barrett, A.J., and Watts, C. (1998). An asparaginyl endopeptidase processes a microbial antigen for class II MHC presentation. Nature 396, 695–699.10.1038/25379Suche in Google Scholar PubMed
Mansour, A.M., Drevs, J., Esser, N., Hamada, F.M., Badary, O.A., Unger, C., Fichtner, I., and Kratz, F. (2003). A new approach for the treatment of malignant melanoma: enhanced antitumor efficacy of an albumin-binding doxorubicin prodrug that is cleaved by matrix metalloproteinase 2. Cancer Res. 63, 4062–4066.Suche in Google Scholar
Mason, S.D. and Joyce, J.A. (2011). Proteolytic networks in cancer. Trends Cell Biol. 21, 228–237.10.1016/j.tcb.2010.12.002Suche in Google Scholar PubMed PubMed Central
McIntyre, J.O., Fingleton, B., Wells, K.S., Piston, D.W., Lynch, C.C., Gautam, S., and Matrisian, L.M. (2004). Development of a novel fluorogenic proteolytic beacon for in vivo detection and imaging of tumour-associated matrix metalloproteinase-7 activity. Biochem. J. 377, 617–628.10.1042/bj20030582Suche in Google Scholar
Mikhaylov, G., Mikac, U., Magaeva, A.A., Itin, V.I., Naiden, E.P., Psakhye, I., Babes, L., Reinheckel, T., Peters, C., Zeiser, R., et al. (2011). Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and their microenvironment. Nat. Nanotechnol. 6, 594–602.10.1038/nnano.2011.112Suche in Google Scholar PubMed
Mikhaylov, G., Klimpel, D., Schaschke, N., Mikac, U., Vizovisek, M., Fonovic, M., Turk, V., Turk, B., and Vasiljeva, O. (2014). Selective targeting of tumor and stromal cells by a nanocarrier system displaying lipidated cathepsin B inhibitor. Angew. Chem. Int. Ed. 53, 10077–10081.10.1002/anie.201402305Suche in Google Scholar PubMed PubMed Central
Min, H.Y., Doyle, L.V., Vitt, C.R., Zandonella, C.L., Stratton-Thomas, J.R., Shuman, M.A., and Rosenberg, S. (1996). Urokinase receptor antagonists inhibit angiogenesis and primary tumor growth in syngeneic mice. Cancer Res. 56, 2428–2433.Suche in Google Scholar
Miyake, H., Hara, I., and Eto, H. (2004). Serum level of cathepsin B and its density in men with prostate cancer as novel markers of disease progression. Anticancer Res. 24, 2573–2577.Suche in Google Scholar
Mohamed, M.M. and Sloane, B.F. (2006). Cysteine cathepsins: multifunctional enzymes in cancer. Nat. Rev. Cancer 6, 764–775.10.1038/nrc1949Suche in Google Scholar PubMed
Mullooly, M., McGowan, P.M., Crown, J., and Duffy, M.J. (2016). The ADAMs family of proteases as targets for the treatment of cancer. Cancer Biol. Ther. 17, 870–880.10.1080/15384047.2016.1177684Suche in Google Scholar
Murphy, G. (2008). The ADAMs: signalling scissors in the tumour microenvironment. Nat. Rev. Cancer 8, 929–941.10.1038/nrc2459Suche in Google Scholar
Murray, A.S., Varela, F.A., and List, K. (2016). Type II transmembrane serine proteases as potential targets for cancer therapy. Biol. Chem. 397, 815–826.10.1515/hsz-2016-0131Suche in Google Scholar
Murthy, R.V., Arbman, G., Gao, J., Roodman, G.D., and Sun, X.F. (2005). Legumain expression in relation to clinicopathologic and biological variables in colorectal cancer. Clin. Cancer Res. 11, 2293–2299.10.1158/1078-0432.CCR-04-1642Suche in Google Scholar
Nagai, A., Terashima, M., Harada, T., Shimode, K., Takeuchi, H., Murakawa, Y., Nagasaki, M., Nakano, A., and Kobayashi, S. (2003). Cathepsin B and H activities and cystatin C concentrations in cerebrospinal fluid from patients with leptomeningeal metastasis. Clin. Chim. Acta 329, 53–60.10.1016/S0009-8981(03)00023-8Suche in Google Scholar
Olson, O.C. and Joyce, J.A. (2015). Cysteine cathepsin proteases: regulators of cancer progression and therapeutic response. Nat. Rev. Cancer 15, 712–729.10.1038/nrc4027Suche in Google Scholar
Ossowski, L., Russo-Payne, H., and Wilson, E.L. (1991). Inhibition of urokinase-type plasminogen activator by antibodies: the effect on dissemination of a human tumor in the nude mouse. Cancer Res. 51, 274–281.Suche in Google Scholar
Page-McCaw, A., Serano, J., Sante, J.M., and Rubin, G.M. (2003). Drosophila matrix metalloproteinases are required for tissue remodeling, but not embryonic development. Dev. Cell 4, 95–106.10.1016/S1534-5807(02)00400-8Suche in Google Scholar
Parks, W.C., Wilson, C.L., and Lopez-Boado, Y.S. (2004). Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat. Rev. Immunol. 4, 617–629.10.1038/nri1418Suche in Google Scholar PubMed
Persson, M., Skovgaard, D., Brandt-Larsen, M., Christensen, C., Madsen, J., Nielsen, C.H., Thurison, T., Klausen, T.L., Holm, S., Loft, A., et al. (2015). First-in-human uPAR PET: imaging of cancer aggressiveness. Theranostics 5, 1303–1316.10.7150/thno.12956Suche in Google Scholar PubMed PubMed Central
Puente, X.S., Sanchez, L.M., Overall, C.M., and Lopez-Otin, C. (2003). Human and mouse proteases: a comparative genomic approach. Nat. Rev. Genet. 4, 544–558.10.1038/nrg1111Suche in Google Scholar PubMed
Rawlings, N.D. and Barrett, A.J. (2000). MEROPS: the peptidase database. Nucleic Acids Res. 28, 323–325.10.1093/nar/28.1.323Suche in Google Scholar PubMed PubMed Central
Rozhin, J., Sameni, M., Ziegler, G., and Sloane, B.F. (1994). Pericellular pH affects distribution and secretion of cathepsin B in malignant cells. Cancer Res. 54, 6517–6525.Suche in Google Scholar
Scorilas, A., Fotiou, S., Tsiambas, E., Yotis, J., Kotsiandri, F., Sameni, M., Sloane, B.F., and Talieri, M. (2002). Determination of cathepsin B expression may offer additional prognostic information for ovarian cancer patients. Biol. Chem. 383, 1297–1303.10.1515/BC.2002.146Suche in Google Scholar PubMed
Sevenich, L. and Joyce, J.A. (2014). Pericellular proteolysis in cancer. Genes Dev. 28, 2331–2347.10.1101/gad.250647.114Suche in Google Scholar PubMed PubMed Central
Seymour, L.W., Ferry, D.R., Kerr, D.J., Rea, D., Whitlock, M., Poyner, R., Boivin, C., Hesslewood, S., Twelves, C., Blackie, R., et al. (2009). Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer. Int. J. Oncol. 34, 1629–1636.10.3892/ijo_00000293Suche in Google Scholar PubMed
Shi, L., De Paoli, V., Rosenzweig, N., and Rosenzweig, Z. (2006). Synthesis and application of quantum dots FRET-based protease sensors. J. Am. Chem. Soc. 128, 10378–10379.10.1021/ja063509oSuche in Google Scholar PubMed
Shimizu, M., Cohen, B., Goldvasser, P., Berman, H., Virtanen, C., and Reedijk, M. (2011). Plasminogen activator uPA is a direct transcriptional target of the JAG1-Notch receptor signaling pathway in breast cancer. Cancer Res. 71, 277–286.10.1158/0008-5472.CAN-10-2523Suche in Google Scholar PubMed
Skelly, M.M., Troy, A., Duffy, M.J., Mulcahy, H.E., Duggan, C., Connell, T.G., O’Donoghue, D.P., and Sheahan, K. (1997). Urokinase-type plasminogen activator in colorectal cancer: relationship with clinicopathological features and patient outcome. Clin. Cancer Res. 3, 1837–1840.Suche in Google Scholar
Sobotic, B., Vizovisek, M., Vidmar, R., Van Damme, P., Gocheva, V., Joyce, J.A., Gevaert, K., Turk, V., Turk, B., and Fonovic, M. (2015). Proteomic identification of cysteine cathepsin substrates shed from the surface of cancer cells. Mol. Cell Proteomics 14, 2213–2228.10.1074/mcp.M114.044628Suche in Google Scholar PubMed PubMed Central
Spira, A.I., Middleton, M.R., Naing, A., Autio, K.A., Nemunaitis, J.J., Bendell, J.C., Gordon, M., Humphrey, R.W., Wong, C., and Rizvi, N.A. (2017). PROCLAIM-001: A first-in-human trial to assess tolerability of the protease-activatable anti-PD-L1 Probody CX-072 in solid tumors and lymphomas. J. Clin. Oncol. 35, TPS3107.10.1200/JCO.2017.35.15_suppl.TPS3107Suche in Google Scholar
Stern, L., Perry, R., Ofek, P., Many, A., Shabat, D., and Satchi-Fainaro, R. (2009). A novel antitumor prodrug platform designed to be cleaved by the endoprotease legumain. Bioconjug. Chem. 20, 500–510.10.1021/bc800448uSuche in Google Scholar PubMed
Suzuki, M., Kobayashi, H., Kanayama, N., Saga, Y., Suzuki, M., Lin, C.Y., Dickson, R.B., and Terao, T. (2004). Inhibition of tumor invasion by genomic down-regulation of matriptase through suppression of activation of receptor-bound pro-urokinase. J. Biol. Chem. 279, 14899–14908.10.1074/jbc.M313130200Suche in Google Scholar PubMed
Szabo, R. and Bugge, T.H. (2008). Type II transmembrane serine proteases in development and disease. Int. J. Biochem. Cell Biol. 40, 1297–1316.10.1016/j.biocel.2007.11.013Suche in Google Scholar PubMed
Szarvas, T., vom Dorp, F., Ergun, S., and Rubben, H. (2011). Matrix metalloproteinases and their clinical relevance in urinary bladder cancer. Nat. Rev. Urol. 8, 241–254.10.1038/nrurol.2011.44Suche in Google Scholar PubMed
Talieri, M., Papadopoulou, S., Scorilas, A., Xynopoulos, D., Arnogianaki, N., Plataniotis, G., Yotis, J., and Agnanti, N. (2004). Cathepsin B and cathepsin D expression in the progression of colorectal adenoma to carcinoma. Cancer Lett. 205, 97–106.10.1016/j.canlet.2003.09.033Suche in Google Scholar PubMed
Tipton, K.A., Chan, C., Wong, K.R., Singson, V., Richardson, J.H., Kavanaugh, W.M., Irving, B.A., and West, J.W. (2016). Abstract 3211: PD-1-targeted Probody therapeutics provide anti-tumor efficacy and a 10-fold dose protection against systemic autoimmunity in preclinical studies. Cancer Res. 76, 3211–3211.10.1158/1538-7445.AM2016-3211Suche in Google Scholar
Trouet, A., Masquelier, M., Baurain, R., and Deprez-De Campeneere, D. (1982). A covalent linkage between daunorubicin and proteins that is stable in serum and reversible by lysosomal hydrolases, as required for a lysosomotropic drug-carrier conjugate: in vitro and in vivo studies. Proc. Natl. Acad. Sci. USA 79, 626–629.10.1073/pnas.79.2.626Suche in Google Scholar PubMed PubMed Central
Turk, B. (2006). Targeting proteases: successes, failures and future prospects. Nat. Rev. Drug Discov. 5, 785–799.10.1038/nrd2092Suche in Google Scholar PubMed
Turk, V., Stoka, V., Vasiljeva, O., Renko, M., Sun, T., Turk, B., and Turk, D. (2012). Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim. Biophys. Acta 1824, 68–88.10.1016/j.bbapap.2011.10.002Suche in Google Scholar PubMed PubMed Central
Ueki, N., Lee, S., Sampson, N.S., and Hayman, M.J. (2013). Selective cancer targeting with prodrugs activated by histone deacetylases and a tumour-associated protease. Nat. Commun. 4, 2735.10.1038/ncomms3735Suche in Google Scholar PubMed
Ulisse, S., Baldini, E., Mottolese, M., Sentinelli, S., Gargiulo, P., Valentina, B., Sorrenti, S., Di Benedetto, A., De Antoni, E., and D’Armiento, M. (2010). Increased expression of urokinase plasminogen activator and its cognate receptor in human seminomas. BMC Cancer 10, 151.10.1186/1471-2407-10-151Suche in Google Scholar PubMed PubMed Central
Unkart, J.T., Chen, S.L., Wapnir, I.L., Gonzalez, J.E., Harootunian, A., and Wallace, A.M. (2017). Intraoperative tumor detection using a ratiometric activatable fluorescent peptide: a first-in-human phase 1 study. Ann. Surg. Oncol. 24, 3167–3173.10.1245/s10434-017-5991-3Suche in Google Scholar PubMed
Vadon-Le Goff, S., Hulmes, D.J., and Moali, C. (2015). BMP-1/tolloid-like proteinases synchronize matrix assembly with growth factor activation to promote morphogenesis and tissue remodeling. Matrix Biol. 44–46, 14–23.10.1016/j.matbio.2015.02.006Suche in Google Scholar PubMed
van Rijt, S.H., Bolukbas, D.A., Argyo, C., Datz, S., Lindner, M., Eickelberg, O., Konigshoff, M., Bein, T., and Meiners, S. (2015). Protease-mediated release of chemotherapeutics from mesoporous silica nanoparticles to ex vivo human and mouse lung tumors. ACS Nano 9, 2377–2389.10.1021/nn5070343Suche in Google Scholar PubMed
Vasiljeva, O. and Turk, B. (2008). Dual contrasting roles of cysteine cathepsins in cancer progression: apoptosis versus tumour invasion. Biochimie 90, 380–386.10.1016/j.biochi.2007.10.004Suche in Google Scholar PubMed
Vasiljeva, O., Papazoglou, A., Kruger, A., Brodoefel, H., Korovin, M., Deussing, J., Augustin, N., Nielsen, B.S., Almholt, K., Bogyo, M., et al. (2006). Tumor cell-derived and macrophage-derived cathepsin B promotes progression and lung metastasis of mammary cancer. Cancer Res. 66, 5242–5250.10.1158/0008-5472.CAN-05-4463Suche in Google Scholar PubMed
Vasiljeva, O., Reinheckel, T., Peters, C., Turk, D., Turk, V., and Turk, B. (2007). Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Curr. Pharm. Des. 13, 387–403.10.2174/138161207780162962Suche in Google Scholar PubMed
Watermann, I., Gerspach, J., Lehne, M., Seufert, J., Schneider, B., Pfizenmaier, K., and Wajant, H. (2007). Activation of CD95L fusion protein prodrugs by tumor-associated proteases. Cell Death Differ. 14, 765–774.10.1038/sj.cdd.4402051Suche in Google Scholar PubMed
Watts, C., Matthews, S.P., Mazzeo, D., Manoury, B., and Moss, C.X. (2005). Asparaginyl endopeptidase: case history of a class II MHC compartment protease. Immunol. Rev. 207, 218–228.10.1111/j.0105-2896.2005.00312.xSuche in Google Scholar PubMed
Weaver, A.Y., Singh, S., DuPage, A., Sagert, J., Flandez, J., Menendez, E., Ford, J., Krimm, M., Moore, S., Nguyen, M., et al. (2015). Abstract C165: Development of a probody drug conjugate (PDC) against CD166 for the treatment of multiple cancers. Mol. Cancer Ther. 14, C165.10.1158/1535-7163.TARG-15-C165Suche in Google Scholar
Weidle, U.H., Tiefenthaler, G., and Georges, G. (2014). Proteases as activators for cytotoxic prodrugs in antitumor therapy. Cancer Genomics Proteomics 11, 67–79.Suche in Google Scholar
Welman, A., Sproul, D., Mullen, P., Muir, M., Kinnaird, A.R., Harrison, D.J., Faratian, D., Brunton, V.G., and Frame, M.C. (2012). Diversity of matriptase expression level and function in breast cancer. PLoS One 7, e34182.10.1371/journal.pone.0034182Suche in Google Scholar PubMed PubMed Central
West, J.L. and Hubbell, J.A. (1999). Polymeric biomaterials with degradation sites for proteases involved in cell migration. Macromolecules 32, 241–244.10.1021/ma981296kSuche in Google Scholar
Whitley, M.J., Cardona, D.M., Lazarides, A.L., Spasojevic, I., Ferrer, J.M., Cahill, J., Lee, C.L., Snuderl, M., Blazer 3rd, D.G., Hwang, E.S., et al. (2016). A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer. Sci. Transl. Med. 8, 320ra324.10.1126/scitranslmed.aad0293Suche in Google Scholar
Wong, K.R., Menendez, E., Craik, C.S., Kavanaugh, W.M., and Vasiljeva, O. (2016). In vivo imaging of protease activity by Probody therapeutic activation. Biochimie 122, 62–67.10.1016/j.biochi.2015.11.003Suche in Google Scholar
Xing, R.H., Mazar, A., Henkin, J., and Rabbani, S.A. (1997). Prevention of breast cancer growth, invasion, and metastasis by antiestrogen tamoxifen alone or in combination with urokinase inhibitor B-428. Cancer Res. 57, 3585–3593.Suche in Google Scholar
Xu, Y., Geng, J., An, P., Xu, Y., Huang, J., Lu, W., Liu, S., and Yu, J. (2015). Cathepsin B-sensitive cholesteryl hemisuccinate–gemcitabine prodrug nanoparticles: enhanced cellular uptake and intracellular drug controlled release. RSC Advances 5, 6985–6992.10.1039/C4RA13870HSuche in Google Scholar
Yang, J.L., Seetoo, D., Wang, Y., Ranson, M., Berney, C.R., Ham, J.M., Russell, P.J., and Crowe, P.J. (2000). Urokinase-type plasminogen activator and its receptor in colorectal cancer: independent prognostic factors of metastasis and cancer-specific survival and potential therapeutic targets. Int. J. Cancer 89, 431–439.10.1002/1097-0215(20000920)89:5<431::AID-IJC6>3.0.CO;2-VSuche in Google Scholar
Yim, J.J., Tholen, M., Klaassen, A., Sorger, J., and Bogyo, M. (2018). Optimization of a protease activated probe for optical surgical navigation. Mol. Pharm. 15, 750–758.10.1021/acs.molpharmaceut.7b00822Suche in Google Scholar
Zhang, Y., So, M.K., and Rao, J. (2006). Protease-modulated cellular uptake of quantum dots. Nano Lett. 6, 1988–1992.10.1021/nl0611586Suche in Google Scholar
Zhong, Y.J., Shao, L.H., and Li, Y. (2013). Cathepsin B-cleavable doxorubicin prodrugs for targeted cancer therapy. Int. J. Oncol. 42, 373–383.10.3892/ijo.2012.1754Suche in Google Scholar
Zoratti, G.L., Tanabe, L.M., Varela, F.A., Murray, A.S., Bergum, C., Colombo, E., Lang, J.E., Molinolo, A.A., Leduc, R., Marsault, E., et al. (2015). Targeting matriptase in breast cancer abrogates tumour progression via impairment of stromal-epithelial growth factor signalling. Nat. Commun. 6, 6776.10.1038/ncomms7776Suche in Google Scholar
© 2019 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Reviews
- The multifaceted roles of tumor-associated proteases and harnessing their activity for prodrug activation
- Retrograde response by reactive oxygen/nitrogen species in plants involving different cellular organelles
- Molecular effects of dietary fatty acids on brain insulin action and mitochondrial function
- STRIPAK, a highly conserved signaling complex, controls multiple eukaryotic cellular and developmental processes and is linked with human diseases
- Research Articles/Short Communications
- Cell Biology and Signaling
- Zinc-induced activation of GPR39 regulates glucose homeostasis through glucose-dependent insulinotropic polypeptide secretion from enteroendocrine K-cells
- Long non-coding RNA CHRF promotes proliferation and mesenchymal transition (EMT) in prostate cancer cell line PC3 requiring up-regulating microRNA-10b
- LncRNA DYNLRB2-2 inhibits THP-1 macrophage foam cell formation by enhancing autophagy
- Geniposide alleviates lipopolysaccharide (LPS)-induced inflammation by downregulation of miR-27a in rat pancreatic acinar cell AR42J
- Tripterine inhibits proliferation, migration and invasion of breast cancer MDA-MB-231 cells by up-regulating microRNA-15a
- miR-99b-3p is induced by vitamin D3 and contributes to its antiproliferative effects in gastric cancer cells by targeting HoxD3
Artikel in diesem Heft
- Frontmatter
- Reviews
- The multifaceted roles of tumor-associated proteases and harnessing their activity for prodrug activation
- Retrograde response by reactive oxygen/nitrogen species in plants involving different cellular organelles
- Molecular effects of dietary fatty acids on brain insulin action and mitochondrial function
- STRIPAK, a highly conserved signaling complex, controls multiple eukaryotic cellular and developmental processes and is linked with human diseases
- Research Articles/Short Communications
- Cell Biology and Signaling
- Zinc-induced activation of GPR39 regulates glucose homeostasis through glucose-dependent insulinotropic polypeptide secretion from enteroendocrine K-cells
- Long non-coding RNA CHRF promotes proliferation and mesenchymal transition (EMT) in prostate cancer cell line PC3 requiring up-regulating microRNA-10b
- LncRNA DYNLRB2-2 inhibits THP-1 macrophage foam cell formation by enhancing autophagy
- Geniposide alleviates lipopolysaccharide (LPS)-induced inflammation by downregulation of miR-27a in rat pancreatic acinar cell AR42J
- Tripterine inhibits proliferation, migration and invasion of breast cancer MDA-MB-231 cells by up-regulating microRNA-15a
- miR-99b-3p is induced by vitamin D3 and contributes to its antiproliferative effects in gastric cancer cells by targeting HoxD3