Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (2024)

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Abstract List of references Publications that cite this publication References

Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (1) https://doi.org/10.1158/1535-7163.mct-11-0006 · Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (2) Full text

Journal: Molecular Cancer Therapeutics, 2011, №10, p.1918-1928

Publisher: American Association for Cancer Research (AACR)

Authors:

  1. Matthias Maak
  2. Ulrich Nitsche
  3. Larissa Keller
  4. Petra Wolf
  5. Marianne Sarr
  6. Marine Thiebaud
  7. Robert Rosenberg
  8. Rupert Langer
  9. Jörg Kleeff
  10. Helmut Friess
  11. Ludger Johannes
  12. Klaus-Peter Janssen

Abstract

Abstract Pancreatic carcinoma is one of the most aggressive tumor entities, and standard chemotherapy provides only modest benefit. Therefore, specific targeting of pancreatic cancer for early diagnosis and therapeutic intervention is of great interest. We have previously shown that the cellular receptor for Shiga toxin B (STxB), the glycosphingolipid globotriaosylceramide (Gb3 or CD77) is strongly increased in colorectal adenocarcinoma and their metastases. Here, we report an upregulation of Gb3 in pancreatic adenocarcinoma (21 of 27 cases) as compared with matched normal tissue (n = 27). The mean expression was highly significantly increased from 30 ± 16 ng Gb3/mg tissue in normal pancreas to 61 ± 41 ng Gb3/mg tissue (mean ± SD, P = 0.0006), as evidenced by thin layer chromatography. Upregulation of Gb3 levels did not depend on tumor stage or grading and showed no correlation with clinical outcome. Tumor cells and endothelial cells were identified as the source of increased Gb3 expression by immunocytochemistry. Pancreatic cancer cell lines showed rapid intracellular uptake of STxB to the Golgi apparatus, following the retrograde pathway. The therapeutic application of STxB was tested by specific delivery of covalently coupled SN38, an active metabolite of the topoisomerase I inhibitor irinotecan. The cytotoxic effect of the STxB-SN38 compound in pancreatic cancer cell lines was increased more than 100-fold compared with irinotecan. Moreover, this effect was effectively blocked by competing incubation with nonlabeled STxB, showing the specificity of the targeting. Thus, STxB constitutes a promising new tool for specific targeting of pancreatic cancer. Mol Cancer Ther; 10(10); 1918–28. ©2011 AACR.

List of references

  1. Jemal, Cancer statistics, 2009, CA Cancer J Clin, № 59, с. 225
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (3) https://doi.org/10.3322/caac.20006
  2. Brus, Second line therapy for advanced pancreatic adenocarcinoma: where are we and where are we going? Highlights from the “2010 ASCO Annual Meeting”. Chicago, IL, USA. June 4-8, 2010, JOP, № 11, с. 321
  3. Herrmann, Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group, J Clin Oncol, № 25, с. 2212
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (4) https://doi.org/10.1200/JCO.2006.09.0886
  4. Kovbasnjuk, The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer, Proc Natl Acad Sci U S A, № 102, с. 19087
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (5) https://doi.org/10.1073/pnas.0506474102
  5. Falguieres, Human colorectal tumors and metastases express Gb3 and can be targeted by an intestinal pathogen-based delivery tool, Mol Cancer Ther, № 7, с. 2498
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (6) https://doi.org/10.1158/1535-7163.MCT-08-0430
  6. Janssen, In vivo tumor targeting using a novel intestinal pathogen-based delivery approach, Cancer Res, № 66, с. 7230
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (7) https://doi.org/10.1158/0008-5472.CAN-06-0631
  7. Johannes, Shiga toxins–from cell biology to biomedical applications, Nat Rev Microbiol, № 8, с. 105
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (8) https://doi.org/10.1038/nrmicro2279
  8. Lingwood, Globotriaosyl ceramide receptor function - where membrane structure and pathology intersect, FEBS Lett, № 584, с. 1879
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (9) https://doi.org/10.1016/j.febslet.2009.11.089
  9. Muthing, Shiga toxins, glycosphingolipid diversity, and endothelial cell injury, Thromb Haemost, № 101, с. 252
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (10) https://doi.org/10.1160/TH08-05-0317
  10. Sandvig, Protein toxins from plants and bacteria: probes for intracellular transport and tools in medicine, FEBS Lett, № 584, с. 2626
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (11) https://doi.org/10.1016/j.febslet.2010.04.008
  11. Bast, Toxicity and immunogenicity of a verotoxin 1 mutant with reduced globotriaosylceramide receptor binding in rabbits, Infect Immun, № 65, с. 2019
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (12) https://doi.org/10.1128/iai.65.6.2019-2028.1997
  12. Chart, Patients with haemolytic uraemic syndrome caused by Escherichia coli O157: absence of antibodies to Vero cytotoxin 1 (VT1) or VT2, J Clin Pathol, № 46, с. 1053
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (13) https://doi.org/10.1136/jcp.46.11.1053
  13. Distler, Shiga toxin receptor Gb3Cer/CD77: tumor-association and promising therapeutic target in pancreas and colon cancer, PLoS One, № 4, с. e6813
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (14) https://doi.org/10.1371/journal.pone.0006813
  14. Arab, Verotoxin induces apoptosis and the complete, rapid, long-term elimination of human astrocytoma xenografts in nude mice, Oncol Res, № 11, с. 33
  15. El Alaoui, Shiga toxin-mediated retrograde delivery of a topoisomerase I inhibitor prodrug, Angew Chem Int Ed Engl, № 46, с. 6469
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (15) https://doi.org/10.1002/anie.200701270
  16. Ebrahimnejad, Preparation and in vitro evaluation of actively targetable nanoparticles for SN-38 delivery against HT-29 cell lines, Nanomedicine, № 6, с. 478
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (16) https://doi.org/10.1016/j.nano.2009.10.003
  17. Sapra, Novel delivery of SN38 markedly inhibits tumor growth in xenografts, including a camptothecin-11-refractory model, Clin Cancer Res, № 14, с. 1888
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (17) https://doi.org/10.1158/1078-0432.CCR-07-4456
  18. Burtness, Phase II trial of weekly docetaxel/irinotecan combination in advanced pancreatic cancer, Cancer J, № 13, с. 257
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (18) https://doi.org/10.1097/PPO.0b013e31813c1174
  19. de la Fouchardiere, Phase I study of daily irinotecan as a radiation sensitizer for locally advanced pancreatic cancer, Int J Radiat Oncol Biol Phys, № 77, с. 409
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (19) https://doi.org/10.1016/j.ijrobp.2009.05.008
  20. Gebbia, Irinotecan plus bolus/infusional 5-fluorouracil and leucovorin in patients with pretreated advanced pancreatic carcinoma: a multicenter experience of the Gruppo Oncologico Italia Meridionale, Am J Clin Oncol, № 33, с. 461
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (20) https://doi.org/10.1097/COC.0b013e3181b4e3b0
  21. Sobin, TNM, sixth edition: new developments in general concepts and rules, Semin Surg Oncol, № 21, с. 19
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (21) https://doi.org/10.1002/ssu.10017
  22. Johannes, Retrograde transport of KDEL-bearing B-fragment of Shiga toxin, J Biol Chem, № 272, с. 19554
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (22) https://doi.org/10.1074/jbc.272.31.19554
  23. Mallard, Shiga toxin B-subunit as a tool to study retrograde transport, Methods Mol Med, № 73, с. 209
  24. Falguieres, Targeting of Shiga toxin B-subunit to retrograde transport route in association with detergent-resistant membranes, Mol Biol Cell, № 12, с. 2453
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (23) https://doi.org/10.1091/mbc.12.8.2453
  25. Pellizzari, Binding of verocytotoxin 1 to its receptor is influenced by differences in receptor fatty acid content, Biochemistry, № 31, с. 1363
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (24) https://doi.org/10.1021/bi00120a011
  26. Falguieres, Functionally different pools of Shiga toxin receptor, globotriaosyl ceramide, in HeLa cells, FEBS J, № 273, с. 5205
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (25) https://doi.org/10.1111/j.1742-4658.2006.05516.x
  27. Schuller, Shiga toxin binding in normal and inflamed human intestinal mucosa, Microbes Infect, № 9, с. 35
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (26) https://doi.org/10.1016/j.micinf.2006.10.005
  28. Bast, Murine antibody responses to the verotoxin 1 B subunit: demonstration of major histocompatibility complex dependence and an immunodominant epitope involving phenylalanine 30, Infect Immun, № 65, с. 2978
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (27) https://doi.org/10.1128/iai.65.7.2978-2982.1997
  29. Hakomori, Cell adhesion/recognition and signal transduction through glycosphingolipid microdomain, Glycoconj J, № 17, с. 143
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (28) https://doi.org/10.1023/A:1026524820177
  30. Ono, Glycosylation defining cancer cell motility and invasiveness, Glycoconj J, № 20, с. 71
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (29) https://doi.org/10.1023/B:GLYC.0000018019.22070.7d
  31. Johansson, Cisplatin-induced expression of Gb3 enables verotoxin-1 treatment of cisplatin resistance in malignant pleural mesothelioma cells, Br J Cancer, № 102, с. 383
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (30) https://doi.org/10.1038/sj.bjc.6605467
  32. De Rosa, Inhibition of multidrug resistance by adamantylgb3, a globotriaosylceramide analog, J Biol Chem, № 283, с. 4501
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (31) https://doi.org/10.1074/jbc.M705473200
  33. Lingwood, Globotriaosyl ceramide (Gb3) expression in human tumour cells: intracellular trafficking defines a new retrograde transport pathway from the cell surface to the nucleus, which correlates with sensitivity to verotoxin, Acta Biochim Pol, № 45, с. 351
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (32) https://doi.org/10.18388/abp.1998_4230
  34. Miyamoto, Role of Shiga toxin versus H7 flagellin in enterohaemorrhagic Escherichia coli signalling of human colon epithelium in vivo, Cell Microbiol, № 8, с. 869
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (33) https://doi.org/10.1111/j.1462-5822.2005.00673.x
  35. Obrig, Endothelial heterogeneity in Shiga toxin receptors and responses, J Biol Chem, № 268, с. 15484
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (34) https://doi.org/10.1016/S0021-9258(18)82282-7
  36. Heath-Engel, Verotoxin sensitivity of ECV304 cells in vitro and in vivo in a xenograft tumour model: VT1 as a tumour neovascular marker, Angiogenesis, № 6, с. 129
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (35) https://doi.org/10.1023/B:AGEN.0000011799.47529.fd
  37. Lingwood, Verotoxin/globotriaosyl ceramide recognition: angiopathy, angiogenesis and antineoplasia, Biosci Rep, № 19, с. 345
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (36) https://doi.org/10.1023/A:1020299819637
  38. Viel, In vivo tumor targeting by the B-subunit of shiga toxin, Mol Imaging, № 7, с. 239
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (37) https://doi.org/10.2310/7290.2008.00022
  39. Ebrahimnejad, Preparation and characterization of poly lactide-co-glycolide nanoparticles of SN-38, PDA J Pharm Sci Technol, № 63, с. 512
  40. Kunii, Preparation and antitumor characteristics of PLA/(PEG-PPG-PEG) nanoparticles loaded with camptothecin, Eur J Pharm Biopharm, № 67, с. 9
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (38) https://doi.org/10.1016/j.ejpb.2007.01.012
  41. Zhang, Development and characterization of a novel liposome-based formulation of SN-38, Int J Pharm, № 270, с. 93
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (39) https://doi.org/10.1016/j.ijpharm.2003.10.015
  42. Koizumi, Novel SN-38-incorporating polymeric micelles, NK012, eradicate vascular endothelial growth factor-secreting bulky tumors, Cancer Res, № 66, с. 10048
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (40) https://doi.org/10.1158/0008-5472.CAN-06-1605
  43. Nakajima, Synergistic antitumor activity of the novel SN-38-incorporating polymeric micelles, NK012, combined with 5-fluorouracil in a mouse model of colorectal cancer, as compared with that of irinotecan plus 5-fluorouracil, Int J Cancer, № 122, с. 2148
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (41) https://doi.org/10.1002/ijc.23381
  44. Kaye, Shiga toxin-associated hemolytic uremic syndrome: interleukin-1 beta enhancement of Shiga toxin cytotoxicity toward human vascular endothelial cells in vitro, Infect Immun, № 61, с. 3886
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (42) https://doi.org/10.1128/iai.61.9.3886-3891.1993
  45. Taguchi, Verotoxins induce apoptosis in human renal tubular epithelium derived cells, Kidney Int, № 53, с. 1681
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (43) https://doi.org/10.1046/j.1523-1755.1998.00939.x
  46. Ergonul, Shigatoxin-1 binding and receptor expression in human kidneys do not change with age, Pediatr Nephrol, № 18, с. 246
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (44) https://doi.org/10.1007/s00467-002-1025-9
  47. Burris, Assessing clinical benefit in the treatment of pancreas cancer: gemcitabine compared to 5-fluorouracil, Eur J Cancer, № 33, с. S18
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (45) https://doi.org/10.1016/S0959-8049(96)00324-3
  48. Heinemann, Increased survival using platinum analog combined with gemcitabine as compared to single-agent gemcitabine in advanced pancreatic cancer: pooled analysis of two randomized trials, the GERCOR/GISCAD intergroup study and a German multicenter study, Ann Oncol, № 18, с. 1652
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (46) https://doi.org/10.1093/annonc/mdm283
  49. Klapdor, Irinotecan(Campto R): efficacy as third/forth line therapy in advanced pancreatic cancer, Anticancer Res, № 20, с. 5209
  50. Yoo, A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer, Br J Cancer, № 101, с. 1658
    Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit (47) https://doi.org/10.1038/sj.bjc.6605374

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