Human defensins as cancer biomarkers and antitumour molecules

Journal of Proteomics

Volumn 72, Issue 6, 2009, Pages 918-927

  Droin, Nathalie ^a   Hendra, Jean Baptiste ^b   Ducoroy, Patrick ^b   Solary, Eric ^a,b  

^a Chu   (France)

^b CENTRE GEORGES FRANÇOIS LECLERC   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA DEFENSIN; BETA DEFENSIN 1; CCAAT ENHANCER BINDING PROTEIN ALPHA; CHEMOATTRACTANT; INTERLEUKIN 8; PROTEIN C MYB; TRANSCRIPTION FACTOR PU 1; TUMOR SUPPRESSOR PROTEIN;

ADAPTIVE IMMUNITY; ANGIOGENESIS; ANTIMICROBIAL ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; BODY FLUID; CARCINOGENESIS; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DEATH; CHEMOTAXIS; CYTOTOXICITY; DENDRITIC CELL; EPITHELIUM CELL; GENE CLUSTER; GENE DEFA1; GENE DEFA3; GENETIC POLYMORPHISM; HUMAN; IMMUNOHISTOCHEMISTRY; IMMUNOMODULATION; INNATE IMMUNITY; MACROPHAGE; MARKER GENE; MONOCYTE; MUCOSA CELL; NEUTROPHIL GRANULE; NONHUMAN; PANETH CELL; PRIORITY JOURNAL; PROMOTER REGION; SURFACE ENHANCED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; TUMOR CELL; TUMOR GROWTH;

AMINO ACID SEQUENCE; ANIMALS; ANTINEOPLASTIC AGENTS; DEFENSINS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INTESTINES; MOLECULAR SEQUENCE DATA; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; PANETH CELLS; PEPTIDES; SEQUENCE HOMOLOGY, AMINO ACID; SPECTROMETRY, MASS, MATRIX-ASSISTED LASER DESORPTION-IONIZATION; TUMOR MARKERS, BIOLOGICAL;

BACTERIA (MICROORGANISMS);

EID: 67651161910     PISSN: 18743919     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jprot.2009.01.002     Document Type: Article

References (108)

1. Selsted M.E., and Ouellette A.J. Mammalian defensins in the antimicrobial immune response. Nat Immunol 6 (2005) 551-557
2. Lehrer R.I. Multispecific myeloid defensins. Curr Opin Hematol 14 (2007) 16-21
3. Zanetti M. The role of cathelicidins in the innate host defenses of mammals. Curr Issues Mol Biol 7 (2005) 179-196
4. Pazgier M., Hoover D.M., Yang D., Lu W., and Lubkowski J. Human beta-defensins. Cell Mol Life Sci 63 (2006) 1294-1313
5. Selsted M.E. Theta-defensins: cyclic antimicrobial peptides produced by binary ligation of truncated alpha-defensins. Curr Protein Pept Sci 5 (2004) 365-371
6. Bensch K.W., Raida M., Mägert H.J., Schulz-Knappe P., and Forssmann W.G. hBD-1: a novel beta-defensin from human plasma. FEBS Lett 368 (1995) 331-335
7. Muller C.A., Markovic-Lipkovski J., Klatt T., Gamper J., Schwarz G., Beck H., et al. Human alpha-defensins HNPs-1, -2, and -3 in renal cell carcinoma: influences on tumor cell proliferation. Am J Pathol 160 (2002) 1311-1324
8. Lundy F.T., Orr D.F., Gallagher J.R., Maxwell P., Shaw C., Napier S.S., et al. Identification and overexpression of human neutrophil alpha-defensins (human neutrophil peptides 1, 2 and 3) in squamous cell carcinomas of the human tongue. Oral Oncol 40 (2004) 139-144
9. Melle C., Ernst G., Schimmel B., Bleul A., Thieme H., Kaufmann R., et al. Discovery and identification of alpha-defensins as low abundant, tumor-derived serum markers in colorectal cancer. Gastroenterology 129 (2005) 66-73
10. Roesch-Ely M., Nees M., Karsai S., Ruess A., Bogumil R., Warnken U., et al. Proteomic analysis reveals successive aberrations in protein expression from healthy mucosa to invasive head and neck cancer. Oncogene 26 (2007) 54-64
11. Escher N., Spies-Weisshart B., Kaatz M., Melle C., Bleul A., Driesch D., et al. Identification of HNP3 as a tumour marker in CD4+ and CD4- lymphocytes of patients with cutaneous T-cell lymphoma. Eur J Cancer 42 (2006) 249-255
12. Holterman D.A., Diaz J.I., Blackmore P.F., Davis J.W., Schellhammer P.F., Corica A., et al. Overexpression of alpha-defensin is associated with bladder cancer invasiveness. Urol Oncol 24 (2006) 97-108
13. Bullard R.S., Gibson W., Bose S.K., Belgrave J.K., Eaddy A.C., Wright C.J., et al. Functional analysis of the host defense peptide Human Beta Defensin-1: new insight into its potential role in cancer. Mol Immunol 45 (2008) 839-848
14. Albrethsen J., Møller C.H., Olsen J., Raskov H., and Gammeltoft S. Human neutrophil peptides 1, 2 and 3 are biochemical markers for metastatic colorectal cancer. Eur J Cancer 42 (2006) 3057-3064
15. Donald C.D., Sun C.Q., Lim S.D., Macoska J., Cohen C., Amin M.B., et al. Cancer-specific loss of beta-defensin 1 in renal and prostatic carcinomas. Lab Invest 83 (2003) 501-505
16. Valore E.V., and Ganz T. Posttranslational processing of defensins in immature human myeloid cells. Blood 79 (1992) 1538-1544
17. Valore E.V., Martin E., Harwig S.S., and Ganz T. Intramolecular inhibition of human defensin HNP-1 by its propiece. J Clin Invest 97 (1996) 1624-1629
18. Hill C.P., Yee J., Selsted M.E., and Eisenberg D.L. Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization. Science 251 (1991) 1481-1485
19. Rajabi M., de Leeuw E., Pazgier M., Li J., Lubkowski J., and Lu W. The conserved salt bridge in human alpha -defensin 5 is required for its precursor processing and proteolytic stability. J Biol Chem (May 22 2008) [ahead of pub]
20. Barnathan E.S., Raghunath P.N., Tomaszewski J.E., Ganz T., and Cines D.B. Immunohistochemical localization of defensin in human coronary vessels. Am J Pathol 150 (1997) 1009-1020
21. Rodríguez-García M., Oliva H., Climent N., García F., Gatell J.M., and Gallart T. Human immature monocyte-derived dendritic cells produce and secrete alpha-defensins 1-3. J Leukoc Biol 82 (2007) 1143-1146
22. Agerberth B., Charo J., Werr J., Olsson B., Idali F., Lindbom L., et al. The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 96 (2000) 3086-3093
23. Chalifour A., Jeannin P., Gauchat J.F., Blaecke A., Malissard M., N'Guyen T., et al. Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers alpha-defensin production. Blood 104 (2004) 1778-1783
24. Lundy F.T., Orr D.F., Shaw C., Lamey P.J., and Linden G.J. Detection of individual human neutrophil alpha-defensins (human neutrophil peptides 1, 2 and 3) in unfractionated gingival crevicular fluid - a MALDI-MS approach. Mol Immunol 42 (2005) 575-579
25. Ihi T., Nakazato M., Mukae H., and Matsukura S. Elevated concentrations of human neutrophil peptides in plasma, blood, and body fluids from patients with infections. Clin Infect Dis 25 (1997) 1134-1140
26. Cunliffe R.N. Alpha-defensins in the gastrointestinal tract. Mol Immunol 40 (2003) 463-467
27. Wilson C.L., Ouellette A.J., Satchell D.P., Ayabe T., López-Boado Y.S., Stratman J.L., et al. Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 286 (1999) 113-117
28. Salzman N.H., Ghosh D., Huttner K.M., Paterson Y., and Bevins C.L. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 422 (2003) 478-479
29. Wehkamp J., Salzman N.H., Porter E., Nuding S., Weichenthal M., Petras R.E., et al. Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc Natl Acad Sci USA 102 (2005) 18129-18134
30. Wehkamp J., Wang G., Kübler I., Nuding S., Gregorieff A., Schnabel A., et al. The Paneth cell alpha-defensin deficiency of ileal Crohn's disease is linked to Wnt/Tcf-4. J Immunol 179 (2007) 3109-3118
31. Szyk A., Wu Z., Tucker K., Yang D., Lu W., and Lubkowski J. Crystal structures of human alpha-defensins HNP4, HD5, and HD6. Protein Sci 15 (2006) 2749-2760
32. Sørensen O.E., Thapa D.R., Rosenthal A., Liu L., Roberts A.A., and Ganz T. Differential regulation of beta-defensin expression in human skin by microbial stimuli. J Immunol 174 (2005) 4870-4879
33. Sørensen O.E., Thapa D.R., Roupé K.M., Valore E.V., Sjöbring U., Roberts A.A., et al. Injury-induced innate immune response in human skin mediated by transactivation of the epidermal growth factor receptor. J Clin Invest 116 (2006) 1878-1885
34. Voss E., Wehkamp J., Wehkamp K., Stange E.F., Schröder J.M., and Harder J. NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2. J Biol Chem 281 (2006) 2005-2011
35. Hollox E.J., Armour J.A., and Barber J.C. Extensive normal copy number variation of a beta-defensin antimicrobial-gene cluster. Am J Hum Genet 73 (2003) 591-600
36. Taudien S., Galgoczy P., Huse K., Reichwald K., Schilhabel M., Szafranski K., et al. Polymorphic segmental duplications at 8p23.1 challenge the determination of individual defensin gene repertoires and the assembly of a contiguous human reference sequence. BMC Genomics 5 (2004) 92
37. Mars W.M., Patmasiriwat P., Maity T., Huff V., Weill M.M., and Saunders G.F. Inheritance of unequal numbers of the genes encoding the human neutrophil defensins HP-1 and HP-3. J Biol Chem 270 (1995) 30371-30376
38. Aldred P.M., Hollox E.J., and Armour J.A. Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3. Hum Mol Genet 14 (2005) 2045-2052
39. Linzmeier R.M., and Ganz T. Human defensin gene copy number polymorphisms: comprehensive analysis of independent variation in alpha- and beta-defensin regions at 8p22-p23. Genomics 86 (2005) 423-430
40. Vankeerberghen A., Scudiero O., De Boeck K., Macek Jr. M., Pignatti P.F., Van Hul N., et al. Distribution of human beta-defensin polymorphisms in various control and cystic fibrosis populations. Genomics 85 (2005) 574-581
41. Chen Q., Book M., Fang X., Hoeft A., and Stuber F. Screening of copy number polymorphisms in human beta-defensin genes using modified real-time quantitative PCR. J Immunol Methods 308 (2006) 231-240
42. Semple C.A., Taylor K., Eastwood H., Barran P.E., and Dorin J.R. Beta-defensin evolution: selection complexity and clues for residues of functional importance. Biochem Soc Trans 34 (2006) 257-262
43. Schutte B.C., Mitros J.P., Bartlett J.A., Walters J.D., Jia H.P., Welsh M.J., et al. Discovery of five conserved beta-defensin gene clusters using a computational search strategy. Proc Natl Acad Sci U S A 99 (2002) 2129-2133
44. Hollox E.J., Huffmeier U., Zeeuwen P.L., Palla R., Lascorz J., Rodijk-Olthuis D., et al. Psoriasis is associated with increased beta-defensin genomic copy number. Nat Genet 40 (2008) 23-25
45. Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 3 (2003) 710-720
46. Daher K.A., Lehrer R.I., Ganz T., and Kronenberg M. Isolation and characterization of human defensin cDNA clones. Proc Natl Acad Sci U S A 85 (1988) 7327-7331
47. Bateman A., Singh A., Shustik C., Mars W.M., and Solomon S. The isolation and identification of multiple forms of the neutrophil granule peptides from human leukemic cells. J Biol Chem 266 (1991) 7524-7530
48. Herwig S., Su Q., Zhang W., Ma Y., and Tempst P. Distinct temporal patterns of defensin mRNA regulation during drug-induced differentiation of human myeloid leukemia cells. Blood 87 (1996) 350-364
49. Tsutsumi-Ishii Y., Hasebe T., and Nagaoka I. Role of CCAAT/enhancer-binding protein site in transcription of human neutrophil peptide-1 and -3 defensin genes. J Immunol 164 (2000) 3264-3273
50. Ma Y., Su Q., and Tempst P. Differentiation-stimulated activity binds an ETS-like, essential regulatory element in the human promyelocytic defensin-1 promoter. J Biol Chem 273 (1998) 8727-8740
51. Yaneva M., Kippenberger S., Wang N., Su Q., McGarvey M., Nazarian A., et al. PU.1 and a TTTAAA element in the myeloid defensin-1 promoter create an operational TATA box that can impose cell specificity onto TFIID function. J Immunol 176 (2006) 6906-6917
52. Panyutich A.V., Voitenok N.N., Lehrer R.I., and Ganz T. An enzyme immunoassay for human defensins. J Immunol Methods 141 (1991) 149-155
53. Panyutich A.V., Panyutich E.A., Krapivin V.A., Baturevich E.A., and Ganz T. Plasma defensin concentrations are elevated in patients with septicemia or bacterial meningitis. J Lab Clin Med 122 (1993) 202-207
54. Panyutich A., and Ganz T. Activated alpha 2-macroglobulin is a principal defensin-binding protein. Am J Respir Cell Mol Biol 5 (1991) 101-106
55. Panyutich A.V., Szold O., Poon P.H., Tseng Y., and Ganz T. Identification of defensin binding to C1 complement. FEBS Lett 356 (1994) 169-173
56. Thompson L., Turko I., and Murad F. Mass spectrometry-based relative quantification of human neutrophil peptides 1, 2, and 3 from biological samples. Mol Immunol 43 (2006) 1485-1489
57. Zhou L., Huang L.Q., Beuerman R.W., Grigg M.E., Li S.F., Chew F.T., et al. Proteomic analysis of human tears: defensin expression after ocular surface surgery. J Proteome Res 3 (2004) 410-416
58. Hegedus C.M., Skibola C.F., Warner M., Skibola D.R., Alexander D., Lim S., et al. Decreased urinary beta defensin-1 expression as a biomarker of response to arsenic. Toxicol Sci 106 (2008) 74-82
59. Kim C., and Kaufmann S.H. Defensin: a multifunctional molecule lives up to its versatile name. Trends Microbiol 14 (2006) 428-431
60. Klotman M.E., and Chang T.L. Defensins in innate antiviral immunity. Nat Rev Immunol 6 (2006) 447-456
61. Gallo S.A., Wang W., Rawat S.S., Jung G., Waring A.J., Cole A.M., et al. Theta-defensins prevent HIV-1 Env-mediated fusion by binding gp41 and blocking 6-helix bundle formation. J Biol Chem 281 (2006) 18787-18792
62. Buck C.B., Day P.M., Thompson C.D., Lubkowski J., Lu W., Lowy D.R., et al. Human alpha-defensins block papillomavirus infection. Proc Natl Acad Sci U S A 103 (2006 31) 1516-1521
63. Chang T.L., Vargas Jr. F.J., DelPortillo A., and Klotman M.E. Dual role of alpha-defensin-1 in anti-HIV-1 innate immunity. J Clin Invest 115 (2005) 765-773
64. Zhang L., Yu W., He T., Yu J., Caffrey R.E., Dalmasso E.A., et al. Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science 298 5595 (Nov 1 2002) 995-1000
65. Feng Z., Dubyak G.R., Lederman M.M., and Weinberg A. Cutting edge: human beta defensin 3-a novel antagonist of the HIV-1 coreceptor CXCR4. J Immunol 177 (2006) 782-786
66. Kim C., Gajendran N., Mittrücker H.W., Weiwad M., Song Y.H., Hurwitz R., et al. Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences. Proc Natl Acad Sci U S A 102 (2005) 4830-4835
67. Bokarewa M., and Tarkowski A. Human alpha-defensins neutralize fibrinolytic activity exerted by staphylokinase. Thromb Haemost 91 (2004) 991-999
68. Yang D., Chen Q., Chertov O., and Oppenheim J.J. Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J Leukoc Biol 68 (2000) 9-14
69. Territo M.C., Ganz T., Selsted M.E., and Lehrer R. Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest 84 (1989) 2017-2020
70. Grigat J., Soruri A., Forssmann U., Riggert J., and Zwirner J. Chemoattraction of macrophages, T lymphocytes, and mast cells is evolutionarily conserved within the human alpha-defensin family. J Immunol 179 (2007) 3958-3965
71. van Wetering S., Mannesse-Lazeroms S.P., van Sterkenburg M.A., and Hiemstra P.S. Neutrophil defensins stimulate the release of cytokines by airway epithelial cells: modulation by dexamethasone. Inflamm Res 51 (2002) 8-15
72. Hoover D.M., Boulegue C., Yang D., Oppenheim J.J., Tucker K., Lu W., et al. The structure of human macrophage inflammatory protein-3alpha/CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins. J Biol Chem 277 (2002) 37647-37654
73. Khine A.A., Del Sorbo L., Vaschetto R., Voglis S., Tullis E., Slutsky A.S., et al. Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway. Blood 107 (2006) 2936-2942
74. Syeda F., Liu H.Y., Tullis E., Liu M., Slutsky A.S., and Zhang H. Differential signaling mechanisms of HNP-induced IL-8 production in human lung epithelial cells and monocytes. J Cell Physiol 214 (2008) 820-827
75. Funderburg N., Lederman M.M., Feng Z., Drage M.G., Jadlowsky J., Harding C.V., et al. Human -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2. Proc Natl Acad Sci U S A 104 (2007) 18631-18635
76. Yang D., Chertov O., Bykovskaia S.N., Chen Q., Buffo M.J., Shogan J., et al. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286 (1999) 525-528
77. Biragyn A., Ruffini P.A., Leifer C.A., Klyushnenkova E., Shakhov A., Chertov O., et al. Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 298 (2002) 1025-1029
78. Halder T.M., Bluggel M., Heinzel S., Pawelec G., Meyer H.E., and Kalbacher H. Defensins are dominant HLA-DR-associated self-peptides from CD34(-) peripheral blood mononuclear cells of different tumor patients (plasmacytoma, chronic myeloid leukemia). Blood 95 (2000) 2890-2896
79. van den Berg R.H., Faber-Krol M.C., van Wetering S., Hiemstra P.S., and Daha M.R. Inhibition of activation of the classical pathway of complement by human neutrophil defensins. Blood 92 (1998) 3898-3903
80. Chen X., Niyonsaba F., Ushio H., Hara M., Yokoi H., Matsumoto K., et al. Antimicrobial peptides human beta-defensin (hBD)-3 and hBD-4 activate mast cells and increase skin vascular permeability. Eur J Immunol 37 (2007) 434-444
81. Higazi A.A., Nassar T., Ganz T., Rader D.J., Udassin R., Bdeir K., et al. The alpha-defensins stimulate proteoglycan-dependent catabolism of low-density lipoprotein by vascular cells: a new class of inflammatory apolipoprotein and a possible contributor to atherogenesis. Blood 96 (2000) 1393-1398
82. Nassar T., Akkawi S., Bar-Shavit R., Haj-Yehia A., Bdeir K., Al-Mehdi A.B., et al. Human alpha-defensin regulates smooth muscle cell contraction: a role for low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. Blood 100 (2002) 4026-4032
83. Zou H., Harrington J.J., Sugumar A., Klatt K.K., Smyrk T.C., and Ahlquist D.A. Detection of colorectal disease by stool defensin assay: an exploratory study. Clin Gastroenterol Hepatol 5 (2007) 865-868
84. Bateman A., Singh A., Jothy S., Fraser R., Esch F., and Solomon S. The levels and biologic action of the human neutrophil granule peptide HP-1 in lung tumors. Peptides 13 (1992) 133-139
85. Nam M.J., Kee M.K., Kuick R., and Hanash S.M. Identification of defensin alpha6 as a potential biomarker in colon adenocarcinoma. J Biol Chem 280 (2005) 8260-8265
86. Li J., Zhao J., Yu X., Lange J., Kuerer H., Krishnamurthy S., et al. Identification of biomarkers for breast cancer in nipple aspiration and ductal lavage fluid. Clin Cancer Res 11 (2005) 8312-8320
87. Hubert P., Herman L., Maillard C., Caberg J.H., Nikkels A., Pierard G., et al. Defensins induce the recruitment of dendritic cells in cervical human papillomavirus-associated (pre)neoplastic lesions formed in vitro and transplanted in vivo. FASEB J 21 (2007) 2765-2775
88. Aarbiou J., Tjabringa G.S., Verhoosel R.M., Ninaber D.K., White S.R., Peltenburg L.T., et al. Mechanisms of cell death induced by the neutrophil antimicrobial peptides alpha-defensins and LL-37. Inflamm Res 55 (2006) 119-127
89. Lichtenstein A., Ganz T., Selsted M.E., and Lehrer R.I. In vitro tumor cell cytolysis mediated by peptide defensins of human and rabbit granulocytes. Blood 68 (1986) 1407-1410
90. Economopoulou M., Bdeir K., Cines D.B., Fogt F., Bdeir Y., Lubkowski J., et al. Inhibition of pathologic retinal neovascularization by alpha-defensins. Blood 106 (2005) 3831-3838
91. Chavakis T., Cines D.B., Rhee J.S., Liang O.D., Schubert U., Hammes H.P., et al. Regulation of neovascularization by human neutrophil peptides (alpha-defensins): a link between inflammation and angiogenesis. FASEB J 18 (2004) 1306-1308
92. Sun C.Q., Arnold R., Fernandez-Golarz C., Parrish A.B., Almekinder T., He J., et al. Human beta-defensin-1, a potential chromosome 8p tumor suppressor: control of transcription and induction of apoptosis in renal cell carcinoma. Cancer Res 66 (2006) 8542-8549
93. Gambichler T., Skrygan M., Huyn J., Bechara F.G., Sand M., Altmeyer P., et al. Pattern of mRNA expression of beta-defensins in basal cell carcinoma. BMC Cancer 6 (2006) 163
94. Shnitsar V.M., Lisovskiy I.L., Soldatkina M.A., Nespryadko S.V., Turchak O.V., Vinnitskaya A.B., et al. Human beta-defensin 3 (hBD-3) expression in A431 cell line and human vulval tumors. Exp Oncol 26 4 (2004 Dec) 328-330
95. Pazgier M., Li X., Lu W., and Lubkowski J. Human defensins: synthesis and structural properties. Curr Pharm Des 13 (2007) 3096-3118
96. Biragyn A. Defensins: nonantibiotic use for vaccine development. Curr Protein Pept Sci 6 (2005) 53-60
97. Tani K., Murphy W.J., Chertov O., Salcedo R., Koh C.Y., Utsunomiya I., et al. Defensins act as potent adjuvants that promote cellular and humoral immune responses in mice to a lymphoma idiotype and carrier antigens. Int Immunol 12 (2000) 691-700
98. Gera J.F., and Lichtenstein A. Human neutrophil peptide defensins induce single strand DNA breaks in target cells. Cell Immunol 138 (1991) 108-120
99. Mader J.S., and Hoskin D.W. Cationic antimicrobial peptides as novel cytotoxic agents for cancer treatment. Expert Opin Investig Drugs 8 (2006) 933-946
100. Barker E., and Reisfeld R.A. A mechanism for neutrophil-mediated lysis of human neuroblastoma cells. Cancer Res 53 (1993) 362-367
101. McKeown S.T., Lundy F.T., Nelson J., Lockhart D., Irwin C.R., Cowan C.G., et al. The cytotoxic effects of human neutrophil peptide-1 (HNP1) and lactoferrin on oral squamous cell carcinoma (OSCC) in vitro. Oral Oncol 42 7 (Aug 2006) 685-690
102. Ghavami S., Asoodeh A., Klonisch T., Halayko A.J., Kadkhoda K., Kroczak T.J., et al. Brevinin-2R(1) semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway. J Cell Mol Med 12 (2008) 1005-1022
103. Ma X.T., Xu B., An L.L., Dong C.Y., Lin Y.M., Shi Y., et al. Vaccine with beta-defensin 2-transduced leukemic cells activates innate and adaptive immunity to elicit potent antileukemia responses. Cancer Res 66 (2006) 1169-1176
104. Xu B., Dong C.Y., Zhang F., Lin Y.M., Wu K.F., and Ma X.T. Synergistic antileukemia effect of combinational gene therapy using murine beta-defensin 2 and IL-18 in L1210 murine leukemia model. Gene Ther 14 (2007) 1181-1187
105. Wang Y.S., Wang G.Q., Wen Y.J., Wang L., Chen X.C., Chen P., et al. Immunity against tumor angiogenesis induced by a fusion vaccine with murine beta-defensin 2 and mFlk-1. Clin Cancer Res 13 (2007) 6779-6787
106. Xu N., Wang Y.S., Pan W.B., Xiao B., Wen Y.J., Chen X.C., et al. Human alpha-defensin-1 inhibits growth of human lung adenocarcinoma xenograft in nude mice. Mol Cancer Ther 7 (2008) 1588-1597
107. Conejo-Garcia J.R., Benencia F., Courreges M.C., Kang E., Mohamed-Hadley A., Buckanovich R.J., et al. Tumor-infiltrating dendritic cell precursors recruited by a beta-defensin contribute to vasculogenesis under the influence of Vegf-A. Nat Med 10 (2004) 950-958
108. Zeya H.I., and Spitznagel J.K. Antimicrobial specificity of leukocyte lysosomal cationic proteins. Science 154 (1966) 1049-1051