Shiga toxin and its use in targeted cancer therapy and imaging

Microbial Biotechnology

Volumn 4, Issue 1, 2011, Pages 32-46

  Engedal, Nikolai ^a,b   Skotland, Tore ^a,b   Torgersen, Maria L ^a,b   Sandvig, Kirsten ^a,b,c  

^a OSLO UNIVERSITY HOSPITAL   (Norway)

^b UNIVERSITY OF OSLO   (Norway)

^c UNIVERSITY OF OSLO   (Norway)

Author keywords

[No Author keywords available]

Indexed keywords

GLYCOSPHINGOLIPID; GLYCOSPHINGOLIPID GLOBOTRIAOSYLCERAMIDE; SHIGA TOXIN; TECHNETIUM 99M; UNCLASSIFIED DRUG;

CANCER THERAPY; FLOW CYTOMETRY; FLUORESCENCE MICROSCOPY; HIGH PERFORMANCE THIN LAYER CHROMATOGRAPHY; HUMAN; INTRACELLULAR TRANSPORT; MASS SPECTROMETRY; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; THIN LAYER CHROMATOGRAPHY;

ANIMALS; BIOLOGICAL TRANSPORT; DRUG DELIVERY SYSTEMS; GLOBOSIDES; HUMANS; MOLECULAR IMAGING; NEOPLASMS; SHIGA TOXIN; TRIHEXOSYLCERAMIDES;

ESCHERICHIA COLI; SHIGELLA DYSENTERIAE;

EID: 79951921424     PISSN: 17517907     EISSN: 17517915     Source Type: Journal    
DOI: 10.1111/j.1751-7915.2010.00180.x     Document Type: Review

References (99)

1. Amessou, M., Carrez, D., Patin, D., Sarr, M., Grierson, D.S., Croisy, A., etal. (2008) Retrograde delivery of photosensitizer (TPPp-O-beta-GluOH)3 selectively potentiates its photodynamic activity. Bioconjug Chem 19: 532-538.
2. Arab, S., and Lingwood, C.A. (1996) Influence of phospholipid chain length on verotoxin/globotriaosyl ceramide binding in model membranes: comparison of a supported bilayer film and liposomes. Glycoconj J 13: 159-166.
3. Arab, S., and Lingwood, C.A. (1998) Intracellular targeting of the endoplasmic reticulum/nuclear envelope by retrograde transport may determine cell hypersensitivity to verotoxin via globotriaosyl ceramide fatty acid isoform traffic. J Cell Physiol 177: 646-660.
4. Arab, S., Russel, E., Chapman, W.B., Rosen, B., and Lingwood, C.A. (1997) Expression of the verotoxin receptor glycolipid, globotriaosylceramide, in ovarian hyperplasias. Oncol Res 9: 553-563.
5. Arab, S., Murakami, M., Dirks, P., Boyd, B., Hubbard, S.L., Lingwood, C.A., and Rutka, J.T. (1998) Verotoxins inhibit the growth of and induce apoptosis in human astrocytoma cells. J Neurooncol 40: 137-150.
6. Arab, S., Rutka, J., and Lingwood, C. (1999) Verotoxin induces apoptosis and the complete, rapid, long-term elimination of human astrocytoma xenografts in nude mice. Oncol Res 11: 33-39.
7. Berg, K., Folini, M., Prasmickaite, L., Selbo, P.K., Bonsted, A., Engesaeter, B.O., etal. (2007) Photochemical internalization: a new tool for drug delivery. Curr Pharm Biotechnol 8: 362-372.
8. Boerlin, P., McEwen, S.A., Boerlin-Petzold, F., Wilson, J.B., Johnson, R.P., and Gyles, C.L. (1999) Associations between virulence factors of Shiga toxin-producing Escherichia coli and disease in humans. J Clin Microbiol 37: 497-503.
9. Cooling, L.L., Walker, K.E., Gille, T., and Koerner, T.A. (1998) Shiga toxin binds human platelets via globotriaosylceramide (Pk antigen) and a novel platelet glycosphingolipid. Infect Immun 66: 4355-4366.
10. Cooling, L.L., Zhang, D.S., Naides, S.J., and Koerner, T.A. (2003) Glycosphingolipid expression in acute nonlymphocytic leukemia: common expression of shiga toxin and parvovirus B19 receptors on early myeloblasts. Blood 101: 711-721.
11. Dahle, J., and Larsen, R.H. (2008) Targeted alpha-particle therapy with 227Th-labeled antibodies. Curr Radiopharm 1: 209-214.
12. Damke, H., Baba, T., van der Bliek, A.M., and Schmid, S.L. (1995) Clathrin-independent pinocytosis is induced in cells overexpressing a temperature-sensitive mutant of dynamin. J Cell Biol 131: 69-80.
13. Dancey, G., Begent, R.H., and Meyer, T. (2009) Imaging in targeted delivery of therapy to cancer. Target Oncol 4: 201-217.
14. Distler, U., Souady, J., Hulsewig, M., Drmic-Hofman, I., Haier, J., Friedrich, A.W., etal. (2009) Shiga toxin receptor Gb3Cer/CD77: tumor- association and promising therapeutic target in pancreas and colon cancer. PLoS ONE 4: e6813.
15. El Alaoui, A., Schmidt, F., Amessou, M., Sarr, M., Decaudin, D., Florent, J.C., and Johannes, L. (2007) Shiga toxin-mediated retrograde delivery of a topoisomerase I inhibitor prodrug. Angew Chem Int Ed Engl 46: 6469-6472.
16. Falguières, T., Mallard, F., Baron, C., Hanau, D., Lingwood, C., Goud, B., etal. (2001) Targeting of Shiga toxin B-subunit to retrograde transport route in association with detergent-resistant membranes. Mol Biol Cell 12: 2453-2468.
17. Falguières, T., Maak, M., von Weyhern, C., Sarr, M., Sastre, X., Poupon, M.F., etal. (2008) Human colorectal tumors and metastases express Gb3 and can be targeted by an intestinal pathogen-based delivery tool. Mol Cancer Ther 7: 2498-2508.
18. Farkas-Himsley, H., Hill, R., Rosen, B., Arab, S., and Lingwood, C.A. (1995) The bacterial colicin active against tumor cells in vitro and in vivo is verotoxin 1. Proc Natl Acad Sci USA 92: 6996-7000.
19. Garred, O., van Deurs, B., and Sandvig, K. (1995) Furin-induced cleavage and activation of Shiga toxin. J Biol Chem 270: 10817-10821.
20. Gregory, C.D., Edwards, C.F., Milner, A., Wiels, J., Lipinski, M., Rowe, M., etal. (1988) Isolation of a normal B cell subset with a Burkitt-like phenotype and transformation in vitro with Epstein-Barr virus. Int J Cancer 42: 213-220.
21. Hakomori, S. (1989) Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens. Adv Cancer Res 52: 257-331.
22. Hakomori, S. (1996) Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. Cancer Res 56: 5309-5318.
23. Hakomori, S.I. (2008) Structure and function of glycosphingolipids and sphingolipids: recollections and future trends. Biochim Biophys Acta 1780: 325-346.
24. Hakomori, S., and Zhang, Y. (1997) Glycosphingolipid antigens and cancer therapy. Chem Biol 4: 97-104.
25. Hansen, C.G., Bright, N.A., Howard, G., and Nichols, B.J. (2009) SDPR induces membrane curvature and functions in the formation of caveolae. Nat Cell Biol 11: 807-814.
26. Heath-Engel, H.M., and Lingwood, C.A. (2003) Verotoxin sensitivity of ECV304 cells in vitro and in vivo in a xenograft tumour model: VT1 as a tumour neovascular marker. Angiogenesis 6: 129-141.
27. Hughes, A.K., Ergonul, Z., Stricklett, P.K., and Kohan, D.E. (2002) Molecular basis for high renal cell sensitivity to the cytotoxic effects of shigatoxin-1: upregulation of globotriaosylceramide expression. J Am Soc Nephrol 13: 2239-2245.
28. Ishitoya, S., Kurazono, H., Nishiyama, H., Nakamura, E., Kamoto, T., Habuchi, T., etal. (2004) Verotoxin induces rapid elimination of human renal tumor xenografts in SCID mice. J Urol 171: 1309-1313.
29. Ito, M., Suzuki, E., Naiki, M., Sendo, F., and Arai, S. (1984) Carbohydrates as antigenic determinants of tumor-associated antigens recognized by monoclonal anti-tumor antibodies produced in a syngeneic system. Int J Cancer 34: 689-697.
30. Jacewicz, M.S., Mobassaleh, M., Gross, S.K., Balasubramanian, K.A., Daniel, P.F., Raghavan, S., etal. (1994) Pathogenesis of Shigella diarrhea: XVII. A mammalian cell membrane glycolipid, Gb3, is required but not sufficient to confer sensitivity to Shiga toxin. J Infect Dis 169: 538-546.
31. Janssen, K.P., Vignjevic, D., Boisgard, R., Falguières, T., Bousquet, G., Decaudin, D., etal. (2006) In vivo tumor targeting using a novel intestinal pathogen-based delivery approach. Cancer Res 66: 7230-7236.
32. Johannes, L., and Popoff, V. (2008) Tracing the retrograde route in protein trafficking. Cell 135: 1175-1187.
33. Johannes, L., and Römer, W. (2010) Shiga toxins - from cell biology to biomedical applications. Nat Rev Microbiol 8: 105-116.
34. Johansson, D., Johansson, A., Grankvist, K., Andersson, U., Henriksson, R., Bergstrom, P., etal. (2006) Verotoxin-1 induction of apoptosis in Gb3-expressing human glioma cell lines. Cancer Biol Ther 5: 1211-1217.
35. Johansson, D., Kosovac, E., Moharer, J., Ljuslinder, I., Brannstrom, T., Johansson, A., and Behnam-Motlagh, P. (2009) Expression of verotoxin-1 receptor Gb3 in breast cancer tissue and verotoxin-1 signal transduction to apoptosis. BMC Cancer 9: 67.
36. van de Kar, N.C., Monnens, L.A., Karmali, M.A., and van Hinsbergh, V.W. (1992) Tumor necrosis factor and interleukin-1 induce expression of the verocytotoxin receptor globotriaosylceramide on human endothelial cells: implications for the pathogenesis of the hemolytic uremic syndrome. Blood 80: 2755-2764.
37. Khan, F., Proulx, F., and Lingwood, C.A. (2009) Detergent-resistant globotriaosyl ceramide may define verotoxin/glomeruli-restricted hemolytic uremic syndrome pathology. Kidney Int 75: 1209-1216.
38. Khine, A.A., and Lingwood, C.A. (1994) Capping and receptor-mediated endocytosis of cell-bound verotoxin (Shiga-like toxin). 1: chemical identification of an amino acid in the B subunit necessary for efficient receptor glycolipid binding and cellular internalization. J Cell Physiol 161: 319-332.
39. Kovbasnjuk, O., Mourtazina, R., Baibakov, B., Wang, T., Elowsky, C., Choti, M.A., etal. (2005) The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer. Proc Natl Acad Sci USA 102: 19087-19092.
40. LaCasse, E.C., Saleh, M.T., Patterson, B., Minden, M.D., and Gariepy, J. (1996) Shiga-like toxin purges human lymphoma from bone marrow of severe combined immunodeficient mice. Blood 88: 1561-1567.
41. LaCasse, E.C., Bray, M.R., Patterson, B., Lim, W.M., Perampalam, S., Radvanyi, L.G., etal. (1999) Shiga-like toxin-1 receptor on human breast cancer, lymphoma, and myeloma and absence from CD34(+) hematopoietic stem cells: implications for ex vivo tumor purging and autologous stem cell transplantation. Blood 94: 2901-2910.
42. Lauvrak, S.U., Torgersen, M.L., and Sandvig, K. (2004) Efficient endosome-to-Golgi transport of Shiga toxin is dependent on dynamin and clathrin. J Cell Sci 117: 2321-2331.
43. Lauvrak, S.U., Walchli, S., Iversen, T.G., Slagsvold, H.H., Torgersen, M.L., Spilsberg, B., and Sandvig, K. (2006) Shiga toxin regulates its entry in a Syk-dependent manner. Mol Biol Cell 17: 1096-1109.
44. Lee, S.Y., Lee, M.S., Cherla, R.P., and Tesh, V.L. (2008) Shiga toxin 1 induces apoptosis through the endoplasmic reticulum stress response in human monocytic cells. Cell Microbiol 10: 770-780.
45. Lin, J.H. (1998) Applications and limitations of interspecies scaling and in vitro extrapolation in pharmacokinetics. Drug Metab Dispos 26: 1202-1212.
46. Ling, H., Boodhoo, A., Hazes, B., Cummings, M.D., Armstrong, G.D., Brunton, J.L., and Read, R.J. (1998) Structure of the shiga-like toxin I B-pentamer complexed with an analogue of its receptor Gb3. Biochemistry 37: 1777-1788.
47. Lingwood, C.A. (1994) Verotoxin-binding in human renal sections. Nephron 66: 21-28.
48. Lingwood, C.A. (1999) Verotoxin/globotriaosyl ceramide recognition: angiopathy, angiogenesis and antineoplasia. Biosci Rep 19: 345-354.
49. Lingwood, C.A., Binnington, B., Manis, A., and Branch, D.R. (2010a) Globotriaosyl ceramide receptor function - Where membrane structure and pathology intersect. FEBS Lett 584: 1879-1886.
50. Lingwood, C.A., Manis, A., Mahfoud, R., Khan, F., Binnington, B., and Mylvaganam, M. (2010b) New aspects of the regulation of glycosphingolipid receptor function. Chem Phys Lipids 163: 27-35.
51. Mangeney, M., Richard, Y., Coulaud, D., Tursz, T., and Wiels, J. (1991) CD77: an antigen of germinal center B cells entering apoptosis. Eur J Immunol 21: 1131-1140.
52. Mangeney, M., Lingwood, C.A., Taga, S., Caillou, B., Tursz, T., and Wiels, J. (1993) Apoptosis induced in Burkitt's lymphoma cells via Gb3/CD77, a glycolipid antigen. Cancer Res 53: 5314-5319.
53. Miyamoto, Y., Iimura, M., Kaper, J.B., Torres, A.G., and Kagnoff, M.F. (2006) Role of Shiga toxin versus H7 flagellin in enterohaemorrhagic Escherichia coli signalling of human colon epithelium in vivo. Cell Microbiol 8: 869-879.
54. Moreland, J.L., Gramada, A., Buzko, O.V., Zhang, Q., and Bourne, P.E. (2005) The Molecular Biology Toolkit (MBT): a modular platform for developing molecular visualization applications. BMC Bioinformatics 6: 21.
55. Murray, L.J., Habeshaw, J.A., Wiels, J., and Greaves, M.F. (1985) Expression of Burkitt lymphoma-associated antigen (defined by the monoclonal antibody 38.13) on both normal and malignant germinal-centre B cells. Int J Cancer 36: 561-565.
56. Müthing, J., and Distler, U. (2010) Advances on the compositional analysis of glycosphingolipids combining thin-layer chromatography with mass spectrometry. Mass Spectrom Rev 129: 425-479.
57. Nichols, B.J., Kenworthy, A.K., Polishchuk, R.S., Lodge, R., Roberts, T.H., Hirschberg, K., etal. (2001) Rapid cycling of lipid raft markers between the cell surface and Golgi complex. J Cell Biol 153: 529-541.
58. Nudelman, E., Kannagi, R., Hakomori, S., Parsons, M., Lipinski, M., Wiels, J., etal. (1983) A glycolipid antigen associated with Burkitt lymphoma defined by a monoclonal antibody. Science 220: 509-511.
59. Nyholm, P.G., Magnusson, G., Zheng, Z., Norel, R., Binnington-Boyd, B., and Lingwood, C.A. (1996) Two distinct binding sites for globotriaosyl ceramide on verotoxins: identification by molecular modelling and confirmation using deoxy analogues and a new glycolipid receptor for all verotoxins. Chem Biol 3: 263-275.
60. Obata, F., Tohyama, K., Bonev, A.D., Kolling, G.L., Keepers, T.R., Gross, L.K., etal. (2008) Shiga toxin 2 affects the central nervous system through receptor globotriaosylceramide localized to neurons. J Infect Dis 198: 1398-1406.
61. Ohyama, C., Fukushi, Y., Satoh, M., Saitoh, S., Orikasa, S., Nudelman, E., etal. (1990) Changes in glycolipid expression in human testicular tumor. Int J Cancer 45: 1040-1044.
62. Ohyama, C., Orikasa, S., Satoh, M., Saito, S., Ohtani, H., and Fukushi, Y. (1992) Globotriaosyl ceramide glycolipid in seminoma: its clinicopathological importance in differentiation from testicular malignant lymphoma. J Urol 148: 72-75.
63. Palermo, M.S., Exeni, R.A., and Fernandez, G.C. (2009) Hemolytic uremic syndrome: pathogenesis and update of interventions. Expert Rev Anti Infect Ther 7: 697-707.
64. Pellizzari, A., Pang, H., and Lingwood, C.A. (1992) Binding of verocytotoxin 1 to its receptor is influenced by differences in receptor fatty acid content. Biochemistry 31: 1363-1370.
65. Peter, M.G., and Lingwood, C.A. (2000) Apparent cooperativity in multivalent verotoxin-globotriaosyl ceramide binding: kinetic and saturation binding studies with [(125)I]verotoxin. Biochim Biophys Acta 1501: 116-124.
66. Phelps, M.E. (2000) PET: the merging of biology and imaging into molecular imaging. J Nucl Med 41: 661-681.
67. Pina, D.G., Johannes, L., and Castanho, M.A. (2007) Shiga toxin B-subunit sequential binding to its natural receptor in lipid membranes. Biochim Biophys Acta 1768: 628-636.
68. Proulx, F., Seidman, E.G., and Karpman, D. (2001) Pathogenesis of Shiga toxin-associated hemolytic uremic syndrome. Pediatr Res 50: 163-171.
69. Raa, H., Grimmer, S., Schwudke, D., Bergan, J., Walchli, S., Skotland, T., etal. (2009) Glycosphingolipid requirements for endosome-to-Golgi transport of Shiga toxin. Traffic 10: 868-882.
70. Ramegowda, B., Samuel, J.E., and Tesh, V.L. (1999) Interaction of Shiga toxins with human brain microvascular endothelial cells: cytokines as sensitizing agents. J Infect Dis 180: 1205-1213.
71. Römer, W., Berland, L., Chambon, V., Gaus, K., Windschiegl, B., Tenza, D., etal. (2007) Shiga toxin induces tubular membrane invaginations for its uptake into cells. Nature 450: 670-675.
72. Rutjes, N.W., Binnington, B.A., Smith, C.R., Maloney, M.D., and Lingwood, C.A. (2002) Differential tissue targeting and pathogenesis of verotoxins 1 and 2 in the mouse animal model. Kidney Int 62: 832-845.
73. Saint-Pol, A., Yelamos, B., Amessou, M., Mills, I.G., Dugast, M., Tenza, D., etal. (2004) Clathrin adaptor epsinR is required for retrograde sorting on early endosomal membranes. Dev Cell 6: 525-538.
74. Salhia, B., Rutka, J.T., Lingwood, C., Nutikka, A., and Van Furth, W.R. (2002) The treatment of malignant meningioma with verotoxin. Neoplasia 4: 304-311.
75. Sandvig, K., Olsnes, S., Brown, J.E., Petersen, O.W., and van Deurs, B. (1989) Endocytosis from coated pits of Shiga toxin: a glycolipid-binding protein from Shigella dysenteriae 1. J Cell Biol 108: 1331-1343.
76. Sandvig, K., Garred, O., Prydz, K., Kozlov, J.V., Hansen, S.H., and van Deurs, B. (1992) Retrograde transport of endocytosed Shiga toxin to the endoplasmic reticulum. Nature 358: 510-512.
77. Sandvig, K., Bergan, J., Dyve, A.B., Skotland, T., and Torgersen, M.L. (2009) Endocytosis and retrograde transport of Shiga toxin. Toxicon (in press) doi:10.1016/j.toxicon.2009.11.021.
78. Schapiro, F.B., Lingwood, C., Furuya, W., and Grinstein, S. (1998) pH-independent retrograde targeting of glycolipids to the Golgi complex. Am J Physiol 274: C319-C332.
79. Schroeder, G.N., and Hilbi, H. (2008) Molecular pathogenesis of Shigella spp.: controlling host cell signaling, invasion, and death by type III secretion. Clin Microbiol Rev 21: 134-156.
80. Schuller, S., Heuschkel, R., Torrente, F., Kaper, J.B., and Phillips, A.D. (2007) Shiga toxin binding in normal and inflamed human intestinal mucosa. Microbes Infect 9: 35-39.
81. van Setten, P.A., Monnens, L.A., Verstraten, R.G., van den Heuvel, L.P., and van Hinsbergh, V.W. (1996) Effects of verocytotoxin-1 on nonadherent human monocytes: binding characteristics, protein synthesis, and induction of cytokine release. Blood 88: 174-183.
82. van Setten, P.A., van Hinsbergh, V.W., van der Velden, T.J., van de Kar, N.C., Vermeer, M., Mahan, J.D., etal. (1997) Effects of TNF alpha on verocytotoxin cytotoxicity in purified human glomerular microvascular endothelial cells. Kidney Int 51: 1245-1256.
83. Siegler, R.L., Obrig, T.G., Pysher, T.J., Tesh, V.L., Denkers, N.D., and Taylor, F.B. (2003) Response to Shiga toxin 1 and 2 in a baboon model of hemolytic uremic syndrome. Pediatr Nephrol 18: 92-96.
84. Smith, W.E., Kane, A.V., Campbell, S.T., Acheson, D.W., Cochran, B.H., and Thorpe, C.M. (2003) Shiga toxin 1 triggers a ribotoxic stress response leading to p38 and JNK activation and induction of apoptosis in intestinal epithelial cells. Infect Immun 71: 1497-1504.
85. Soltyk, A.M., MacKenzie, C.R., Wolski, V.M., Hirama, T., Kitov, P.I., Bundle, D.R., and Brunton, J.L. (2002) A mutational analysis of the globotriaosylceramide-binding sites of verotoxin VT1. J Biol Chem 277: 5351-5359.
86. Starr, T., Sun, Y., Wilkins, N., and Storrie, B. (2010) Rab33b and Rab6 are functionally overlapping regulators of golgi homeostasis and trafficking. Traffic 11: 626-636.
87. Taga, S., Carlier, K., Mishal, Z., Capoulade, C., Mangeney, M., Lecluse, Y., etal. (1997) Intracellular signaling events in CD77-mediated apoptosis of Burkitt's lymphoma cells. Blood 90: 2757-2767.
88. Tarr, P.I., Gordon, C.A., and Chandler, W.L. (2005) Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 365: 1073-1086.
89. Tarrago-Trani, M.T., Jiang, S., Harich, K.C., and Storrie, B. (2006) Shiga-like toxin subunit B (SLTB)-enhanced delivery of chlorin e6 (Ce6) improves cell killing. Photochem Photobiol 82: 527-537.
90. Tesh, V.L. (2010) Induction of apoptosis by Shiga toxins. Future Microbiol 5: 431-453.
91. Tesh, V.L., Samuel, J.E., Burris, J.A., Owens, J.W., Taylor, F.B., and Siegler, R.L. (1994) Quantitation and localization of shiga toxin/shiga-like toxin-binding glycolipid receptors in human and baboon tissues. In Recent Advances in Verocytotoxin-producing Escherichia coli Infections: Proceedings of the 2nd International Symposium and Workshop on Verocytotoxin-producing Escherichia coli Infections. Karmali, M.A., and Goglio, A.G. (eds). Amsterdam, The Netherlands: Elsevier, pp. 189-192.
92. Tetaud, C., Falguières, T., Carlier, K., Lecluse, Y., Garibal, J., Coulaud, D., etal. (2003) Two distinct Gb3/CD77 signaling pathways leading to apoptosis are triggered by anti-Gb3/CD77 mAb and verotoxin-1. J Biol Chem 278: 45200-45208.
93. Torgersen, M.L., Lauvrak, S.U., and Sandvig, K. (2005) The A-subunit of surface-bound Shiga toxin stimulates clathrin-dependent uptake of the toxin. FEBS J 272: 4103-4113.
94. Torgersen, M.L., Engedal, N., Bergan, J., and Sandvig, K. (2010) The intracellular journey of Shiga toxins. Open Toxinol J 3: 3-12.
95. Viel, T., Dransart, E., Nemati, F., Henry, E., Theze, B., Decaudin, D., etal. (2008) In vivo tumor targeting by the B-subunit of shiga toxin. Mol Imaging 7: 239-247.
96. Weissleder, R., and Pittet, M.J. (2008) Imaging in the era of molecular oncology. Nature 452: 580-589.
97. Wenk, J., Andrews, P.W., Casper, J., Hata, J., Pera, M.F., von Keitz, A., etal. (1994) Glycolipids of germ cell tumors: extended globo-series glycolipids are a hallmark of human embryonal carcinoma cells. Int J Cancer 58: 108-115.
98. Wiels, J., Fellous, M., and Tursz, T. (1981) Monoclonal antibody against a Burkitt lymphoma-associated antigen. Proc Natl Acad Sci USA 78: 6485-6488.
99. Yu, M., and Haslam, D.B. (2005) Shiga toxin is transported from the endoplasmic reticulum following interaction with the luminal chaperone HEDJ/ERdj3. Infect Immun 73: 2524-2532.