Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
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Identification of CEA-interacting proteins in colon cancer cells and their changes in expression after irradiation

  • Yoo, Byong Chul (Colorectal Cancer Branch, Research Institute, National Cancer Center) ;
  • Yeo, Seung-Gu (Department of Radiation Oncology, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine)
  • Received : 2017.05.17
  • Accepted : 2017.07.31
  • Published : 2017.09.30
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Abstract

Purpose: The serum carcinoembryonic antigen (CEA) level has been recognized as a prognostic factor in colorectal cancer, and associated with response of rectal cancer to radiotherapy. This study aimed to identify CEA-interacting proteins in colon cancer cells and observe post-irradiation changes in their expression. Materials and Methods: CEA expression in colon cancer cells was examined by Western blot analysis. Using an anti-CEA antibody or IgG as a negative control, immunoprecipitation was performed in colon cancer cell lysates. CEA and IgG immunoprecipitates were used for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Proteins identified in the CEA immunoprecipitates but not in the IgG immunoprecipitates were selected as CEA-interacting proteins. After radiation treatment, changes in expression of CEA-interacting proteins were monitored by Western blot analysis. Results: CEA expression was higher in SNU-81 cells compared with LoVo cells. The membrane localization of CEA limited the immunoprecipitation results and thus the number of CEA-interacting proteins identified. Only the Ras-related protein Rab-6B and lysozyme C were identified as CEA-interacting proteins in LoVo and SNU-81 cells, respectively. Lysozyme C was detected only in SNU-81, and CEA expression was differently regulated in two cell lines; it was down-regulated in LoVo but up-regulated in SNU-81 in radiation dosage-dependent manner. Conclusion: CEA-mediated radiation response appears to vary, depending on the characteristics of individual cancer cells. The lysozyme C and Rab subfamily proteins may play a role in the link between CEA and tumor response to radiation, although further studies are needed to clarify functional roles of the identified proteins.

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References

  1. Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med 1965;122:467-81. https://doi.org/10.1084/jem.122.3.467
  2. Beauchemin N, Draber P, Dveksler G, et al. Redefined nomenclature for members of the carcinoembryonic antigen family. Exp Cell Res 1999;252:243-9. https://doi.org/10.1006/excr.1999.4610
  3. Thomas P, Toth CA, Saini KS, Jessup JM, Steele G Jr. The structure, metabolism and function of the carcinoembryonic antigen gene family. Biochim Biophys Acta 1990;1032:177-89.
  4. Hammarstrom S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol 1999;9:67-81. https://doi.org/10.1006/scbi.1998.0119
  5. Thomas P, Forse RA, Bajenova O. Carcinoembryonic antigen (CEA) and its receptor hnRNP M are mediators of metastasis and the inflammatory response in the liver. Clin Exp Metastasis 2011;28:923-32. https://doi.org/10.1007/s10585-011-9419-3
  6. Compton C, Fenoglio-Preiser CM, Pettigrew N, Fielding LP. American Joint Committee on Cancer Prognostic Factors Consensus Conference: Colorectal Working Group. Cancer 2000;88:1739-57. https://doi.org/10.1002/(SICI)1097-0142(20000401)88:7<1739::AID-CNCR30>3.0.CO;2-T
  7. Yeo SG, Kim DY, Chang HJ, et al. Reappraisal of pretreatment carcinoembryonic antigen in patients with rectal cancer receiving preoperative chemoradiotherapy. Tumori 2013;99:93-9. https://doi.org/10.1177/030089161309900116
  8. Yeo SG. Preoperative chemoradiotherapy followed by transanal local excision for T3 distal rectal cancer: A case report. Exp Ther Med 2016;11:1465-8. https://doi.org/10.3892/etm.2016.3065
  9. Yeo SG, Kim DY, Oh JH. Long-term survival without surgery following a complete response to pre-operative chemoradiotherapy for rectal cancer: a case series. Oncol Lett 2013;6:1573-6. https://doi.org/10.3892/ol.2013.1596
  10. Kim K, Kim KH, Roh K, et al. Antitumor effects of calgranulin B internalized in human colon cancer cells. Oncotarget 2016;7:20368-80.
  11. Kim KH, Yoo BC, Kim WK, et al. CD133 and CD133-regulated nucleophosmin linked to 5-fluorouracil susceptibility in human colon cancer cell line SW620. Electrophoresis 2014;35:522-32. https://doi.org/10.1002/elps.201300364
  12. Benchimol S, Fuks A, Jothy S, Beauchemin N, Shirota K, Stanners CP. Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell 1989;57:327-34. https://doi.org/10.1016/0092-8674(89)90970-7
  13. Ordonez C, Screaton RA, Ilantzis C, Stanners CP. Human carcinoembryonic antigen functions as a general inhibitor of anoikis. Cancer Res 2000;60:3419-24.
  14. Soeth E, Wirth T, List HJ, et al. Controlled ribozyme targeting demonstrates an antiapoptotic effect of carcinoembryonic antigen in HT29 colon cancer cells. Clin Cancer Res 2001;7:2022-30.
  15. Li Y, Cao H, Jiao Z, et al. Carcinoembryonic antigen interacts with TGF-{beta} receptor and inhibits TGF-{beta} signaling in colorectal cancers. Cancer Res 2010;70:8159-68. https://doi.org/10.1158/0008-5472.CAN-10-1073
  16. Beauchemin N, Arabzadeh A. Carcinoembryonic antigenrelated cell adhesion molecules (CEACAMs) in cancer progression and metastasis. Cancer Metastasis Rev 2013;32:643-71. https://doi.org/10.1007/s10555-013-9444-6
  17. Riesterer O, Milas L, Ang KK. Use of molecular biomarkers for predicting the response to radiotherapy with or without chemotherapy. J Clin Oncol 2007;25:4075-83. https://doi.org/10.1200/JCO.2007.11.8497
  18. Hostetter RB, Augustus LB, Mankarious R, Chi KF, Fan D, Toth C, Thomas P, Jessup JM. Carcinoembryonic antigen as a selective enhancer of colorectal cancer metastasis. J Natl Cancer Inst 1990;82:380-5. https://doi.org/10.1093/jnci/82.5.380
  19. Blumenthal RD, Osorio L, Hayes MK, Horak ID, Hansen HJ, Goldenberg DM. Carcinoembryonic antigen antibody inhibits lung metastasis and augments chemotherapy in a human colonic carcinoma xenograft. Cancer Immunol Immunother 2005;54:315-27. https://doi.org/10.1007/s00262-004-0597-6
  20. Serra C, Vizoso F, Alonso L, et al. Expression and prognostic significance of lysozyme in male breast cancer. Breast Cancer Res 2002;4:R16. https://doi.org/10.1186/bcr537
  21. Yi YF, Huang YR. Arylsulfatase, betagalactosidase and lysozyme in gastric cancer cells and its relationship to invasion. World J Gastroenterol 1998;4:52-54.
  22. Sava G, Benetti A, Ceschia V, Pacor S. Lysozyme and cancer: role of exogenous lysozyme as anticancer agent (review). Anticancer Res 1989;9:583-91.
  23. Mahanta S, Paul S, Srivastava A, Pastor A, Kundu B, Chaudhuri TK. Stable self-assembled nanostructured hen egg white lysozyme exhibits strong anti-proliferative activity against breast cancer cells. Colloids Surf B Biointerfaces 2015;130:237-45. https://doi.org/10.1016/j.colsurfb.2015.04.017
  24. Guo TK, Zhao X, Xie XD, et al. The anti-proliferative effects of recombinant human lysozyme on human gastric cancer cells. J Int Med Res 2007;35:353-60. https://doi.org/10.1177/147323000703500310
  25. Yang XZ, Li XX, Zhang YJ, et al. Rab1 in cell signaling, cancer and other diseases. Oncogene 2016;35:5699-704. https://doi.org/10.1038/onc.2016.81
  26. Ming Z, Guo C, Jiang M, et al. Bioinformatics analysis of Rab GDP dissociation inhibitor beta and its expression in nonsmall cell lung cancer. Diagn Pathol 2014;9:201. https://doi.org/10.1186/s13000-014-0201-0
  27. Ho JR, Chapeaublanc E, Kirkwood L, et al. Deregulation of Rab and Rab effector genes in bladder cancer. PLoS One 2012;7:e39469. https://doi.org/10.1371/journal.pone.0039469
  28. Ye F, Tang H, Liu Q, et al. miR-200b as a prognostic factor in breast cancer targets multiple members of RAB family. J Transl Med 2014;12:17. https://doi.org/10.1186/1479-5876-12-17
  29. Jin L, Huo Y, Zheng Z, et al. Down-regulation of Ras-related protein Rab 5C-dependent endocytosis and glycolysis in cisplatin-resistant ovarian cancer cell lines. Mol Cell Proteomics 2014;13:3138-51. https://doi.org/10.1074/mcp.M113.033217
  30. Zhang T, Sun Q, Liu T, et al. MiR-451 increases radiosensitivity of nasopharyngeal carcinoma cells by targeting ras-related protein 14 (RAB14). Tumour Biol 2014;35:12593-9. https://doi.org/10.1007/s13277-014-2581-x
  31. Shin YK, Yoo BC, Chang HJ, et al. Down-regulation of mitochondrial F1F0-ATP synthase in human colon cancer cells with induced 5-fluorouracil resistance. Cancer Res 2005;65:3162-70. https://doi.org/10.1158/0008-5472.CAN-04-3300