Cancer stem cells: The potential role of autophagy, proteolysis, and cathepsins in glioblastoma stem cells

Tumor Biology

Volumn 39, Issue 3, 2017, Pages 1-13

  Bischof, Joachim ^a   Westhoff, Mike Andrew ^a   Wagner, Johanna Elisabeth ^a   Halatsch, Marc Eric ^a   Trentmann, Stephanie ^a   Knippschild, Uwe ^a   Wirtz, Christian Rainer ^a   Burster, Timo ^a  

^a UNIVERSITY HOSPITAL ULM   (Germany)

Author keywords

autophagy; cathepsin; glioblastoma; Major histocompatibility complex class I

Indexed keywords

ANTINEOPLASTIC AGENT; CATHEPSIN; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; PROTEINASE;

AUTOPHAGY; CANCER CHEMOTHERAPY; CANCER IMMUNOLOGY; CANCER RADIOTHERAPY; CANCER RECURRENCE; CANCER RESISTANCE; CANCER SURVIVAL; CARCINOGENESIS; CELL FUNCTION; CELL SURFACE; CELL SURVIVAL; GLIOBLASTOMA; GLIOMA STEM CELL; HUMAN; METASTASIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN PROCESSING; REGULATORY MECHANISM; REVIEW; TREATMENT RESPONSE; TUMOR ESCAPE; ANIMAL; BRAIN TUMOR; CANCER STEM CELL; METABOLISM; PATHOLOGY;

ANIMALS; AUTOPHAGY; BRAIN NEOPLASMS; CATHEPSINS; GLIOBLASTOMA; HUMANS; NEOPLASTIC STEM CELLS; PROTEOLYSIS;

EID: 85016924033     PISSN: 10104283     EISSN: 14230380     Source Type: Journal    
DOI: 10.1177/1010428317692227     Document Type: Review

References (176)

1. Nature milestones cancer, http://www.Nature.Com/milestones/milecancer/timeline.Html
2. Furth J, Kahn MC., The transmission of leukaemia of mice with a single cell. Am J Cancer 1937; 31: 276–282.
3. Bruce WR, Van Der Gaag H., A quantitative assay for the number of murine lymphoma cells capable of proliferation in vivo. Nature 1963; 199: 79–80.
4. Becker AJ, Mc CE, Till JE., Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 1963; 197: 452–454.
5. Buick RN, Till JE, McCulloch EA., Colony assay for proliferative blast cells circulating in myeloblastic leukaemia. Lancet 1977; 1: 862–863.
6. Lapidot T, Sirard C, Vormoor J. A cell initiating human acute myeloid leukaemia after transplantation into scid mice. Nature 1994; 367: 645–648.
7. Bonnet D, Dick JE., Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997; 3: 730–737.
8. Al-Hajj M, Wicha MS, Benito-Hernandez A. Prospective identification of tumorigenic breast cancer cells. P Natl Acad Sci USA 2003; 100: 3983–3988.
9. Singh SK, Hawkins C, Clarke ID. Identification of human brain tumour initiating cells. Nature 2004; 432: 396–401.
10. Collins AT, Berry PA, Hyde C. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 2005; 65: 10946–10951.
11. Prince ME, Sivanandan R, Kaczorowski A. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. P Natl Acad Sci USA 2007; 104: 973–978.
12. Hermann PC, Huber SL, Herrler T. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 2007; 1: 313–323.
13. O’Brien CA, Pollett A, Gallinger S. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007; 445: 106–110.
14. Wu C, Wei Q, Utomo V. Side population cells isolated from mesenchymal neoplasms have tumor initiating potential. Cancer Res 2007; 67: 8216–8222.
15. Eramo A, Lotti F, Sette G. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 2008; 15: 504–514.
16. Clarke MF, Dick JE, Dirks PB. Cancer stem cells—perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res 2006; 66: 9339–9344.
17. Kreso A, Dick JE., Evolution of the cancer stem cell model. Cell Stem Cell 2014; 14: 275–291.
18. Blanpain C, Mohrin M, Sotiropoulou PA. DNA-damage response in tissue-specific and cancer stem cells. Cell Stem Cell 2011; 8: 16–29.
19. Odoux C, Fohrer H, Hoppo T. A stochastic model for cancer stem cell origin in metastatic colon cancer. Cancer Res 2008; 68: 6932–6941.
20. Hirschmann-Jax C, Foster AE, Wulf GG. A distinct “Side population” of cells with high drug efflux capacity in human tumor cells. P Natl Acad Sci USA 2004; 101: 14228–14233.
21. Ma I, Allan AL., The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev 2011; 7: 292–306.
22. Magee JA, Piskounova E, Morrison SJ., Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer cell 2012; 21: 283–296.
23. Rycaj K, Tang DG., Cell-of-origin of cancer versus cancer stem cells: assays and interpretations. Cancer Res 2015; 75: 4003–4011.
24. Reya T, Morrison SJ, Clarke MF. Stem cells, cancer, and cancer stem cells. Nature 2001; 414: 105–111.
25. Cairns J., Mutation selection and the natural history of cancer. Nature 1975; 255: 197–200.
26. Visvader JE., Cells of origin in cancer. Nature 2011; 469: 314–322.
27. Wu S, Powers S, Zhu W. Substantial contribution of extrinsic risk factors to cancer development. Nature 2016; 529: 43–47.
28. Schneider M, Strobele S, Nonnenmacher L. A paired comparison between glioblastoma “stem cells” and differentiated cells. Int J Cancer 2016; 138(7): 1709–1718.
29. Dahan P, Martinez Gala J, Delmas C. Ionizing radiations sustain glioblastoma cell dedifferentiation to a stem-like phenotype through survivin: possible involvement in radioresistance. Cell Death Dis 2014; 5: e1543.
30. Leder K, Pitter K, Laplant Q. Mathematical modeling of PDGF-driven glioblastoma reveals optimized radiation dosing schedules. Cell 2014; 156: 603–616.
31. Olmez I, Shen W, McDonald H. Dedifferentiation of patient-derived glioblastoma multiforme cell lines results in a cancer stem cell-like state with mitogen-independent growth. J Cell Mol Med 2015; 19: 1262–1272.
32. Beck B, Blanpain C., Unravelling cancer stem cell potential. Nat Rev 2013; 13: 727–738.
33. Gupta PB, Fillmore CM, Jiang G. Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell 2011; 146: 633–644.
34. Klionsky DJ, Emr SD., Autophagy as a regulated pathway of cellular degradation. Science 2000; 290: 1717–1721.
35. Liu B, Wen X, Cheng Y., Survival or death: disequilibrating the oncogenic and tumor suppressive autophagy in cancer. Cell Death Dis 2013; 4: e892.
36. Lorin S, Hamai A, Mehrpour M. Autophagy regulation and its role in cancer. Semin Cancer Biol 2013; 23: 361–379.
37. Liang XH, Jackson S, Seaman M. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999; 402: 672–676.
38. Laddha SV, Ganesan S, Chan CS. Mutational landscape of the essential autophagy gene BECN1 in human cancers. Mol Cancer Res 2014; 12: 485–490.
39. Li Z, Bao S, Wu Q. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 2009; 15: 501–513.
40. Clarke L, van der Kooy D., Low oxygen enhances primitive and definitive neural stem cell colony formation by inhibiting distinct cell death pathways. Stem Cells 2009; 27: 1879–1886.
41. Conley SJ, Gheordunescu E, Kakarala P. Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia. P Natl Acad Sci USA 2012; 109: 2784–2789.
42. Warburg O, Posener K, Negelein E., Ueber den stoffwechsel der tumoren; biochemische zeitschrift. Biochem Z 1924; 152: 319–344.
43. Kim JH, Kim HY, Lee YK. Involvement of mitophagy in oncogenic k-ras-induced transformation: overcoming a cellular energy deficit from glucose deficiency. Autophagy 2011; 7: 1187–1198.
44. Fung C, Lock R, Gao S. Induction of autophagy during extracellular matrix detachment promotes cell survival. Mol Biol Cell 2008; 19: 797–806.
45. Yu L, Strandberg L, Lenardo MJ., The selectivity of autophagy and its role in cell death and survival. Autophagy 2008; 4: 567–573.
46. Cuervo AM, Dice JF., A receptor for the selective uptake and degradation of proteins by lysosomes. Science 1996; 273: 501–503.
47. Dunn WA, Jr. Studies on the mechanisms of autophagy: formation of the autophagic vacuole. J Cell Biol 1990; 110: 1923–1933.
48. Crotzer VL, Blum JS., Autophagy and its role in MHC-mediated antigen presentation. J Immunol 2009; 182: 3335–3341.
49. Baba M, Takeshige K, Baba N. Ultrastructural analysis of the autophagic process in yeast: detection of autophagosomes and their characterization. J Cell Biol 1994; 124: 903–913.
50. Munz C., Enhancing immunity through autophagy. Annu Rev Immunol 2009; 27: 423–449.
51. Pankiv S, Clausen TH, Lamark T. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 2007; 282: 24131–24145.
52. Mizushima N, Yoshimori T., How to interpret LC3 immunoblotting. Autophagy 2007; 3: 542–545.
53. Racoma IO, Meisen WH, Wang QE. Thymoquinone inhibits autophagy and induces cathepsin-mediated, caspase-independent cell death in glioblastoma cells. PLoS ONE 2013; 8: e72882.
54. Bjorkoy G, Lamark T, Brech A. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol 2005; 171: 603–614.
55. Mathew R, Karp CM, Beaudoin B. Autophagy suppresses tumorigenesis through elimination of p62. Cell 2009; 137: 1062–1075.
56. Choi AM, Ryter SW, Levine B., Autophagy in human health and disease. New Engl J Med 2013; 368: 1845–1846.
57. Bonora M, Wieckowsk MR, Chinopoulos C. Molecular mechanisms of cell death: central implication of ATP synthase in mitochondrial permeability transition. Oncogene 2015; 34: 1608.
58. Westhoff MA, Karpel-Massler G, Bruhl O. A critical evaluation of PI3K inhibition in glioblastoma and neuroblastoma therapy. Mol Cell Ther 2014; 2: 32.
59. Inoki K, Zhu T, Guan KL., TSC2 mediates cellular energy response to control cell growth and survival. Cell 2003; 115: 577–590.
60. Takeshige K, Baba M, Tsuboi S. Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Biol 1992; 119: 301–311.
61. Lum JJ, Bauer DE, Kong M. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 2005; 120: 237–248.
62. Stephan JS, Yeh YY, Ramachandran V. The Tor and cAMP-dependent protein kinase signaling pathways coordinately control autophagy in Saccharomyces cerevisiae. Autophagy 2010; 6: 294–295.
63. Jung CH, Jun CB, Ro SH. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 2009; 20: 1992–2003.
64. Hosokawa N, Hara T, Kaizuka T. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell 2009; 20: 1981–1991.
65. Wu X, Fleming A, Ricketts T. Autophagy regulates notch degradation and modulates stem cell development and neurogenesis. Nat Commun 2016; 7: 10533.
66. Natsumeda M, Maitani K, Liu Y. Targeting notch signaling and autophagy increases cytotoxicity in glioblastoma neurospheres. Brain Pathol 2016; 26: 713–723.
67. Glaumann H, Ahlberg J., Comparison of different autophagic vacuoles with regard to ultrastructure, enzymatic composition, and degradation capacity—formation of crinosomes. Exp Mol Pathol 1987; 47: 346–362.
68. Zhao H, Cai Y, Santi S. Chloroquine-mediated radiosensitization is due to the destabilization of the lysosomal membrane and subsequent induction of cell death by necrosis. Radiat Res 2005; 164: 250–257.
69. Yamamoto A, Tagawa Y, Yoshimori T. Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells. Cell Struct Funct 1998; 23: 33–42.
70. Steinman RM, Mellman IS, Muller WA. Endocytosis and the recycling of plasma membrane. J Cell Biol 1983; 96: 1–27.
71. Seglen PO, Grinde B, Solheim AE., Inhibition of the lysosomal pathway of protein degradation in isolated rat hepatocytes by ammonia, methylamine, chloroquine and leupeptin. Eur J Biochem 1979; 95: 215–225.
72. Wibo M, Poole B., Protein degradation in cultured cells. II. The uptake of chloroquine by rat fibroblasts and the inhibition of cellular protein degradation and cathepsin B1. J Cell Biol 1974; 63: 430–440.
73. Chou TF, Brown SJ, Minond D. Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways. P Natl Acad Sci USA 2011; 108: 4834–4839.
74. Wilcox D, Mason RW., Inhibition of cysteine proteinases in lysosomes and whole cells. Biochem J 1992; 285(Pt 2): 495–502.
75. Hoyvik H, Gordon PB, Berg TO. Inhibition of autophagic-lysosomal delivery and autophagic lactolysis by asparagine. J Cell Biol 1991; 113: 1305–1312.
76. Blommaart EF, Krause U, Schellens JP. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur J Biochem 1997; 243: 240–246.
77. Seglen PO, Gordon PB., 3-methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. P Natl Acad Sci USA 1982; 79: 1889–1892.
78. Choi YJ, Park YJ, Park JY. Inhibitory effect of mTOR activator MHY1485 on autophagy: suppression of lysosomal fusion. PLoS ONE 2012; 7: e43418.
79. Grinde B., Effect of carboxylic ionophores on lysosomal protein degradation in rat hepatocytes. Exp Cell Res 1983; 149: 27–35.
80. Underwood BR, Imarisio S, Fleming A. Antioxidants can inhibit basal autophagy and enhance neurodegeneration in models of polyglutamine disease. Hum Mol Genet 2010; 19: 3413–3429.
81. Webb JL, Ravikumar B, Rubinsztein DC., Microtubule disruption inhibits autophagosome-lysosome fusion: implications for studying the roles of aggresomes in polyglutamine diseases. Int J Biochem Cell B 2004; 36: 2541–2550.
82. Reunanen H, Marttinen M, Hirsimaki P., Effects of griseofulvin and nocodazole on the accumulation of autophagic vacuoles in Ehrlich ascites tumor cells. Exp Mol Pathol 1988; 48: 97–102.
83. Deng L, Lei Y, Liu R. Pyrvinium targets autophagy addiction to promote cancer cell death. Cell Death Dis 2013; 4: e614.
84. Egan DF, Chun MG, Vamos M. Small molecule inhibition of the autophagy kinase ULK1 and identification of ULK1 substrates. Mol Cell 2015; 59: 285–297.
85. Liu J, Xia H, Kim M. Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13. Cell 2011; 147: 223–234.
86. Ganley IG, Wong PM, Gammoh N. Distinct autophagosomal-lysosomal fusion mechanism revealed by thapsigargin-induced autophagy arrest. Mol Cell 2011; 42: 731–743.
87. Hoyvik H, Gordon PB, Seglen PO., Use of a hydrolysable probe, [14C]lactose, to distinguish between pre-lysosomal and lysosomal steps in the autophagic pathway. Exp Cell Res 1986; 166: 1–14.
88. Punnonen EL, Reunanen H., Effects of vinblastine, leucine, and histidine, and 3-methyladenine on autophagy in Ehrlich ascites cells. Exp Mol Pathol 1990; 52: 87–97.
89. Munafo DB, Colombo MI., A novel assay to study autophagy: regulation of autophagosome vacuole size by amino acid deprivation. J Cell Sci 2001; 114: 3619–3629.
90. Carew JS, Kelly KR, Nawrocki ST., Autophagy as a target for cancer therapy: new developments. Cancer Manag Res 2012; 4: 357–365.
91. Crombet T, Osorio M, Cruz T. Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients. J Clin Oncol 2004; 22: 1646–1654.
92. Zhuang W, Long L, Zheng B. Curcumin promotes differentiation of glioma-initiating cells by inducing autophagy. Cancer Sci 2012; 103: 684–690.
93. Aoki H, Takada Y, Kondo S. Evidence that curcumin suppresses the growth of malignant gliomas in vitro and in vivo through induction of autophagy: role of Akt and extracellular signal-regulated kinase signaling pathways. Mol Pharmacol 2007; 72: 29–39.
94. Scarlatti F, Maffei R, Beau I. Role of non-canonical beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells. Cell Death Differ 2008; 15: 1318–1329.
95. Wang K, Liu R, Li J. Quercetin induces protective autophagy in gastric cancer cells: involvement of akt-mtor- and hypoxia-induced factor 1alpha-mediated signaling. Autophagy 2011; 7: 966–978.
96. Kim H, Moon JY, Ahn KS. Quercetin induces mitochondrial mediated apoptosis and protective autophagy in human glioblastoma U373MG cells. Oxid Med Cell Longev 2013; 2013: 596496.
97. Behin A, Hoang-Xuan K, Carpentier AF. Primary brain tumours in adults. Lancet 2003; 361: 323–331.
98. Furnari FB, Fenton T, Bachoo RM. Malignant astrocytic glioma: genetics, biology, and paths to treatment. Gene Dev 2007; 21: 2683–2710.
99. Stupp R, van den Bent MJ, Hegi ME., Optimal role of temozolomide in the treatment of malignant gliomas. Curr Neurol Neurosci 2005; 5: 198–206.
100. de Groot JF, Fuller G, Kumar AJ. Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice. Neuro-oncology 2010; 12: 233–242.
101. Delgado-Lopez PD, Corrales-Garcia EM., Survival in glioblastoma: a review on the impact of treatment modalities. Clin Transl Oncol 2016; 18: 1062–1071.
102. Kesari S, Schiff D, Henson JW. Phase ii study of temozolomide, thalidomide, and celecoxib for newly diagnosed glioblastoma in adults. Neuro-oncology 2008; 10: 300–308.
103. Jue TR, McDonald KL., The challenges associated with molecular targeted therapies for glioblastoma. J Neuro-oncol 2016; 127: 427–434.
104. Giese A, Bjerkvig R, Berens ME. Cost of migration: invasion of malignant gliomas and implications for treatment. J Clin Oncol 2003; 21: 1624–1636.
105. Scherer HJ., A critical review: the pathology of cerebral gliomas. J Neurol Psychiatry 1940; 3: 147–177.
106. Pullan S, Wilson J, Metcalfe A. Requirement of basement membrane for the suppression of programmed cell death in mammary epithelium. J Cell Sci 1996; 109(Pt 3): 631–642.
107. Box C, Rogers SJ, Mendiola M. Tumour-microenvironmental interactions: paths to progression and targets for treatment. Semin Cancer Biol 2010; 20: 128–138.
108. Singh SK, Clarke ID, Terasaki M. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003; 63: 5821–5828.
109. Duffy MJ., The role of proteolytic enzymes in cancer invasion and metastasis. Clin Exp Metastas 1992; 10: 145–155.
110. Hambardzumyan D, Bergers G., Glioblastoma: defining tumor niches. Trends Cancer 2015; 1: 252–265.
111. Westhoff MA, Zhou S, Nonnenmacher L. Inhibition of NF-kappaB signaling ablates the invasive phenotype of glioblastoma. Mol Cancer Res 2013; 11: 1611–1623.
112. Li A, Walling J, Kotliarov Y. Genomic changes and gene expression profiles reveal that established glioma cell lines are poorly representative of primary human gliomas. Mol Cancer Res 2008; 6: 21–30.
113. Ortensi B, Setti M, Osti D. Cancer stem cell contribution to glioblastoma invasiveness. Stem Cell Res 2013; 4: 18.
114. De Witt Hamer PC, Van Tilborg AA, Eijk PP. The genomic profile of human malignant glioma is altered early in primary cell culture and preserved in spheroids. Oncogene 2008; 27: 2091–2096.
115. Pollard SM, Yoshikawa K, Clarke ID. Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell 2009; 4: 568–580.
116. Fan X, Salford LG, Widegren B., Glioma stem cells: evidence and limitation. Semin Cancer Biol 2007; 17: 214–218.
117. Lathia JD, Gallagher J, Myers JT. Direct in vivo evidence for tumor propagation by glioblastoma cancer stem cells. PLoS ONE 2011; 6: e24807.
118. Beier CP, Beier D., CD133 negative cancer stem cells in glioblastoma. Front Biosci 2011; 3: 701–710.
119. Kim KJ, Lee KH, Kim HS. The presence of stem cell marker-expressing cells is not prognostically significant in glioblastomas. Neuropathology 2011; 31: 494–502.
120. Liu G, Yuan X, Zeng Z. Analysis of gene expression and chemoresistance of cd133+ cancer stem cells in glioblastoma. Mol Cancer 2006; 5: 67.
121. Burster T., Processing and regulation mechanisms within antigen presenting cells: a possibility for therapeutic modulation. Curr Pharm Design 2013; 19: 13.
122. Dolenc I, Turk B, Pungercic G. Oligomeric structure and substrate induced inhibition of human cathepsin C. J Biol Chem 1995; 270: 21626–21631.
123. Colbert JD, Matthews SP, Miller G. Diverse regulatory roles for lysosomal proteases in the immune response. Eur J Immunol 2009; 39: 2955–2965.
124. Starkey PM, Barrett AJ., Human cathepsin G. Catalytic and immunological properties. Biochem J 1976; 155: 273–278.
125. Mounter LA, Atiyeh W., Proteases of human leukocytes. Blood 1960; 15: 52–59.
126. Burster T, Beck A, Tolosa E. Cathepsin G, and not the asparagine-specific endoprotease, controls the processing of myelin basic protein in lysosomes from human B lymphocytes. J Immunol 2004; 172: 5495–5503.
127. Burster T, Beck A, Tolosa E. Differential processing of autoantigens in lysosomes from human monocyte-derived and peripheral blood dendritic cells. J Immunol 2005; 175: 5940–5949.
128. Lebez D, Kopitar M., Leucocyte proteinases. I. Low molecular weight cathepsins of F and G type. Enzymologia 1970; 39: 271–283.
129. Korkmaz B, Horwitz MS, Jenne DE. Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases. Pharmacol Rev 2010; 62: 726–759.
130. Baggiolini M, Schnyder J, Bretz U. Cellular mechanisms of proteinase release from inflammatory cells and the degradation of extracellular proteins. CIBA F Symp 1979; 75: 105–121.
131. Affara NI, Andreu P, Coussens LM., Delineating protease functions during cancer development. Methods Mol Biol 2009; 539: 1–32.
132. Vandooren J, Opdenakker G, Loadman PM. Proteases in cancer drug delivery. Adv Drug Deliver Rev 2016; 97: 144–155.
133. Gocheva V, Joyce JA., Cysteine cathepsins and the cutting edge of cancer invasion. Cell Cycle 2007; 6: 60–64.
134. Eeckhout Y, Vaes G., Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Effects of lysosomal cathepsin B, plasmin and kallikrein, and spontaneous activation. Biochem J 1977; 166: 21–31.
135. Lakka SS, Gondi CS, Rao JS., Proteases and glioma angiogenesis. Brain Pathol 2005; 15: 327–341.
136. Kobayashi H, Ohi H, Sugimura M. Inhibition of in vitro ovarian cancer cell invasion by modulation of urokinase-type plasminogen activator and cathepsin B. Cancer Res 1992; 52: 3610–3614.
137. Kostoulas G, Lang A, Nagase H. Stimulation of angiogenesis through cathepsin B inactivation of the tissue inhibitors of matrix metalloproteinases. FEBS Lett 1999; 455: 286–290.
138. Rempel SA, Rosenblum ML, Mikkelsen T. Cathepsin B expression and localization in glioma progression and invasion. Cancer Res 1994; 54: 6027–6031.
139. Sivaparvathi M, Sawaya R, Wang SW. Overexpression and localization of cathepsin B during the progression of human gliomas. Clin Exp Metastas 1995; 13: 49–56.
140. Sivaparvathi M, McCutcheon I, Sawaya R. Expression of cysteine protease inhibitors in human gliomas and meningiomas. Clin Exp Metastas 1996; 14: 344–350.
141. Demchik LL, Sameni M, Nelson K. Cathepsin B and glioma invasion. Int J Dev Neurosci 1999; 17: 483–494.
142. Nonnenmacher L, Westhoff MA, Fulda S. Rist: a potent new combination therapy for glioblastoma. Int J Cancer 2015; 136: E173–E187.
143. Palesch D, Wagner J, Meid A. Cathepsin G-mediated proteolytic degradation of MHC class I molecules to facilitate immune detection of human glioblastoma cells. Cancer Immunol Immun 2016; 65: 283–291.
144. Sivaparvathi M, Yamamoto M, Nicolson GL. Expression and immunohistochemical localization of cathepsin l during the progression of human gliomas. Clin Exp Metastas 1996; 14: 27–34.
145. Flannery T, McQuaid S, McGoohan C. Cathepsin S expression: an independent prognostic factor in glioblastoma tumours—a pilot study. Int J Cancer 2006; 119: 854–860.
146. Burden RE, Gormley JA, Jaquin TJ. Antibody-mediated inhibition of cathepsin S blocks colorectal tumor invasion and angiogenesis. Clin Cancer Res 2009; 15: 6042–6051.
147. Flannery T, Gibson D, Mirakhur M. The clinical significance of cathepsin S expression in human astrocytomas. Am J Pathol 2003; 163: 175–182.
148. Schweiger A, Staib A, Werle B. Cysteine proteinase cathepsin H in tumours and sera of lung cancer patients: relation to prognosis and cigarette smoking. Brit J Cancer 2000; 82: 782–788.
149. Sivaparvathi M, Sawaya R, Gokaslan ZL. Expression and the role of cathepsin H in human glioma progression and invasion. Cancer Lett 1996; 104: 121–126.
150. Verbovsek U, Motaln H, Rotter A. Expression analysis of all protease genes reveals cathepsin K to be overexpressed in glioblastoma. PLoS ONE 2014; 9: e111819.
151. Konduri SD, Yanamandra N, Siddique K. Modulation of cystatin c expression impairs the invasive and tumorigenic potential of human glioblastoma cells. Oncogene 2002; 21: 8705–8712.
152. Sienczyk M, Oleksyszyn J., Irreversible inhibition of serine proteases—design and in vivo activity of diaryl alpha-aminophosphonate derivatives. Curr Med Chem 2009; 16: 1673–1687.
153. Miller JF, Brunner KT, Sprent J. Thymus-derived cells as killer cells in cell-mediated immunity. Transplant Proc 1971; 3: 915–917.
154. Kiessling R, Klein E, Wigzell H. “Natural” killer cells in the mouse. I. Cytotoxic cells with specificity for mouse moloney leukemia cells. Specificity and distribution according to genotype. Eur J Immunol 1975; 5: 112–117.
155. Herberman RB, Nunn ME, Lavrin DH. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic acid allogeneic tumors. I. Distribution of reactivity and specificity. Int J Cancer 1975; 16: 216–229.
156. Karre K., Natural killer cell recognition of missing self. Nat Immunol 2008; 9: 477–480.
157. Paust S, von Andrian UH., Natural killer cell memory. Nat Immunol 2011; 12: 500–508.
158. Young JD, Damiano A, DiNome MA. Dissociation of membrane binding and lytic activities of the lymphocyte pore-forming protein (perforin). J Exp Med 1987; 165: 1371–1382.
159. Pahl J, Cerwenka A., Tricking the balance: NK cells in anti-cancer immunity. Immunobiology 2017; 222: 11–20.
160. Blum JS, Wearsch PA, Cresswell P., Pathways of antigen processing. Annu Rev Immunol 2013; 31: 443–473.
161. Edwards KM, Davis JE, Browne KA. Anti-viral strategies of cytotoxic T lymphocytes are manifested through a variety of granule-bound pathways of apoptosis induction. Immunol Cell Biol 1999; 77: 76–89.
162. Neefjes J, Jongsma ML, Paul P. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol 2011; 11: 823–836.
163. Rammensee HG., Peptides made to order. Immunity 2006; 25: 693–695.
164. Adiko AC, Babdor J, Gutierrez-Martinez E. Intracellular transport routes for MHC I and their relevance for antigen cross-presentation. Front Immunol 2015; 6: 335.
165. Gromme M, Uytdehaag FG, Janssen H. Recycling MHC class I molecules and endosomal peptide loading. P Natl Acad Sci USA 1999; 96: 10326–10331.
166. Reid PA, Watts C., Cycling of cell-surface MHC glycoproteins through primaquine-sensitive intracellular compartments. Nature 1990; 346: 655–657.
167. Hochman JH, Jiang H, Matyus L. Endocytosis and dissociation of class I MHC molecules labeled with fluorescent beta-2 microglobulin. J Immunol 1991; 146: 1862–1867.
168. Schirmbeck R, Melber K, Reimann J., Hepatitis B virus small surface antigen particles are processed in a novel endosomal pathway for major histocompatibility complex class I-restricted epitope presentation. Eur J Immunol 1995; 25: 1063–1070.
169. Munz C., Antigen processing for MHC class II presentation via autophagy. Front Immunol 2012; 3: 9.
170. Hewitt EW, : The MHC class I antigen presentation pathway: strategies for viral immune evasion. Immunology 2003; 110: 163–169.
171. Schwartz O, Marechal V, Le Gall S. Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nature Med 1996; 2: 338–342.
172. Seidel UJ, Oliveira CC, Lampen MH. A novel category of antigens enabling CTL immunity to tumor escape variants: Cinderella antigens. Cancer Immunol Immunother 2012; 61: 119–125.
173. Zagzag D, Salnikow K, Chiriboga L. Downregulation of major histocompatibility complex antigens in invading glioma cells: stealth invasion of the brain. Lab Invest 2005; 85: 328–341.
174. Pisklakova A, McKenzie B, Zemp F. M011l-deficient oncolytic myxoma virus induces apoptosis in brain tumor-initiating cells and enhances survival in a novel immunocompetent mouse model of glioblastoma. Neuro-Oncology. Epub ahead of print 8 March 2016. DOI: 10.1093/neuonc/now006.
175. Eipper S, Steiner R, Lesner A. Lactoferrin is an allosteric enhancer of the proteolytic activity of cathepsin G. PLoS ONE 2016; 11: e0151509.
176. Siltari A, Kivimaki AS, Ehlers PI. Effects of milk casein derived tripeptides on endothelial enzymes in vitro; a study with synthetic tripeptides. Arznei-Forschung 2012; 62: 477–481.