Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지

Expression Pattern of Tumor Endothelial Marker 8 Protein in Gallbladder Carcinomas

Maurya, Sanjeev Kumar;Tewari, Mallika;Kumar, Mohan;Thakur, Mahendra Kumar;Shukla, Hari Shanker

  • Published : 20110200
⟨ Previous Next ⟩

Abstract

Tumor endothelial marker 8 protein (TEM8) is highly specific to tumor angiogenesis and is not required for normal adult angiogenesis and hence might prove to be a target for anti-angiogenic therapies in the future. We here evaluated protein and gene expression patterns in human endothelial cells of benign gallbladder - gallstone diseases (GSDs) and gallbladder carcinomas (GBCs) using immunostaining, immunofluorescence and western blotting techniques. Subjects comprised 175 GBC patients, 38 males and 137 females, aged 30-85 years (mean age $50.3{\pm}13.4$ years) and twenty with GSDs, aged 30-75 years, ($51.4{\pm}10.0$ years) for comparison (male 4/20 and females 16/20). TEM8 protein expression increased significantly (p<0.0001) with increasing stage of GBC and was mostly limited to endothelial cells, although there was no significant change with the grade. Interestingly, only 80-85 kDa and 60 kDa isoforms of TEM8 increased significantly whereas 45 kDa isoform was absent in GBCs. Conclusions- These results suggest that TEM8 plays an unknown important biological role to promote tumor angiogenesis in GBC.

Keywords

References

  1. Abrami L, Leppla SH, van der Goot FG (2006). Receptor palmitoylation and ubiquitination regulate anthrax toxin endocytosis. J Cell Biol, 172, 309-20. https://doi.org/10.1083/jcb.200507067
  2. Bonuccelli G, Sotgia F, Frank PG, et al (2005). ATR/TEM8 is highly expressed in epithelial cells lining Bacillus anthracis' three sites of entry: implications for the pathogenesis of anthrax infection. Am J Physiol Cell Physiol, 288, 1402-10. https://doi.org/10.1152/ajpcell.00582.2004
  3. Bradley KA, Mogridge J, Mourez M (2001). Identification of the cellular receptor for anthrax toxin. Nature, 414, 225-9. https://doi.org/10.1038/n35101999
  4. Carson-Walter EB, Watkins DN, Nanda A, et al (2001). Cell surface tumor endothelial markers are conserved in mice and humans. Cancer Res, 61, 6649-55.
  5. Darabos N, Stare R (2004). Gallbladder cancer: laparoscopic and classic cholecystectomy. Surg Endosc, 18, 144-7. https://doi.org/10.1007/s00464-002-9269-9
  6. Davies G, Cunnick GH, Mansel RE, et al (2004). Levels of expression of endothelial markers specific to tumourassociated endothelial cells and their correlation with prognosis in patients with breast cancer. Clin Exp Metastasis, 21, 31-7. https://doi.org/10.1023/B:CLIN.0000017168.83616.d0
  7. Duan HF, Hu XW, Chen JL, et al (2007). Antitumour activities of TEM8-Fc: an engineered antibody-like molecule targeting tumour endothelial marker 8. J Natl Cancer Inst, 99, 1551-5. https://doi.org/10.1093/jnci/djm132
  8. Grant DS, Kleinman HK (1997). Regulation of capillary formation by laminin and other components of the extracellular matrix. EXS, 79, 317-33.
  9. Hotchkiss KA, Basile CM, Spring SC, et al (2005). TEM8 expression stimulates endothelial cell adhesion and migration by regulating cell-matrix interactions on collagen. Exp Cell Res, 305, 133-44. https://doi.org/10.1016/j.yexcr.2004.12.025
  10. HS Shukla (2006). Gallbladder cancer. J Surg Oncol, 93, 604-6. https://doi.org/10.1002/jso.20524
  11. Kalluri R (2003). Angiogenesis: basement membranes: structure, assembly and role in tumour angiogenesis. Nat Rev Cancer, 3, 422-33. https://doi.org/10.1038/nrc1094
  12. Kerbel R, Folkman J (2002). Clinical translation of angiogenesis inhibitors. Nat Rev Cancer, 2, 727-39. https://doi.org/10.1038/nrc905
  13. Lazcano-Ponce EC, Miquel JF, Munoz N, et al (2001). Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin, 51, 349-64. https://doi.org/10.3322/canjclin.51.6.349
  14. Liu S, Leppla SH (2003). Cell surface tumor endothelium marker 8 cytoplasmic tail-independent anthrax toxin binding, proteolytic processing, oligomer formation, and internalization. J Biol Chem, 278, 5227-34. https://doi.org/10.1074/jbc.M210321200
  15. Marneros AG, Olsen BR (2001). The role of collagen-derived proteolytic fragments in angiogenesis. Matrix Biol, 20, 337-45. https://doi.org/10.1016/S0945-053X(01)00151-2
  16. Maurya SK, Tewari M, Thakur MK, et al (2009). Stage dependent expression of MUC1 gallbladder carcinoma. J Cancer Res Exp Oncol, 1, 1-7.
  17. Maurya SK, Tewari M, Shukla SH, et al (2010). Genetic aberration in gallbladder carcinoma. Surg Oncol, Sep 28, doi:10.1016/j.physletb.2003.10.071
  18. Mooney D, Langer R, Ingber D (1995). Cytoskeletal filament assembly and the control of cell spreading and function by extracellular matrix. J Cell Sci, 108, 2311-20.
  19. Nanda A, St Croix B (2004). Tumor endothelial markers: new targets for cancer therapy. Curr Opin Oncol, 16, 44-9. https://doi.org/10.1097/00001622-200401000-00009
  20. Ramey JD, Villareal VA, Ng C, et al (2010). Anthrax toxin receptor 1/tumor endothelial marker 8: mutation of conserved inserted domain residues overrides cytosolic control of protective antigen binding. Biochemistry. 31, 49, 7403-10.
  21. Scobie HM, Rainey GJ, Bradley KA, et al (2003). Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proc Natl Acad Sci U S A, 100, 5170-4. https://doi.org/10.1073/pnas.0431098100
  22. Shukla HS, Awasthi K, Naithani YP, et al (1981). A clinicopathological study of carcinoma of the gall bladder. Indian J Cancer, 18, 198-201.
  23. St Croix B, Rago C, Velculescu V, et al (2000). Genes expressed in human tumor endothelium. Science, 289, 1197-202. https://doi.org/10.1126/science.289.5482.1197
  24. Thijssen VL, Postel R, Brandwijk RJ, et al (2006). Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc Natl Acad Sci U S A, 103, 15975-80. https://doi.org/10.1073/pnas.0603883103
  25. Venanzi FM, Petrini M, Fiammenghi L, et al (2010). Tumor endothelial marker 8 expression levels in dendritic cell-based cancer vaccines are related to clinical outcome. Cancer Immunol Immunother, 59, 27-34. https://doi.org/10.1007/s00262-009-0717-4
  26. Werner E, Kowalczyk AP, Faundez V (2006). Anthrax Toxin Receptor 1/Tumor Endothelium Marker 8 Mediates Cell Spreading by Coupling Extracellular Ligands to the Actin Cytoskeleton. J Biol Chem, 281, 23227-36. https://doi.org/10.1074/jbc.M603676200
  27. Yang MY, Chaudhary A, Seaman S, et al (2010). The cell surface structure of tumor endothelial marker 8 (TEM8) is regulated by the actin cytoskeleton. Biochim Biophys Acta, doi:10.1016/j.physletb.2003.10.071