Journal of the Formosan Medical Association
Volume 109, Issue 5 , Pages 326-337, May 2010

Decreased GRP78 Protein Expression is a Potential Prognostic Marker of Oral Squamous Cell Carcinoma in Taiwan

  • Tze-Ta Huang

      Affiliations

    • Dental Department, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan
    • School of Medicine, Tzu Chi University, Hualian, Taiwan
  • ,
  • Jeff Yi-Fu Chen

      Affiliations

    • Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan
  • ,
  • Chih-En Tseng

      Affiliations

    • Department of Pathology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan
    • School of Medicine, Tzu Chi University, Hualian, Taiwan
  • ,
  • Yu-Chieh Su

      Affiliations

    • Division of Hematology-Oncology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan
    • School of Medicine, Tzu Chi University, Hualian, Taiwan
  • ,
  • Hsu-Chueh Ho

      Affiliations

    • Department of Otolaryngology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan
    • School of Medicine, Tzu Chi University, Hualian, Taiwan
  • ,
  • Moon-Sing Lee

      Affiliations

    • Division of Radiotherapy and Radiooncology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan
    • School of Medicine, Tzu Chi University, Hualian, Taiwan
  • ,
  • Chiou-Tuz Chang

      Affiliations

    • Dental Department, Taichung Veterans General Hospital, Taichung, Taiwan
  • ,
  • Yong-Kie Wong

      Affiliations

    • Dental Department, Taichung Veterans General Hospital, Taichung, Taiwan
  • ,
  • Hau-Ren Chen

      Affiliations

    • Department of Life Science, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Chiayi, Taiwan
    • Corresponding Author InformationCorrespondence to: Dr Hau-Ren Chen, Department of Life Science, Institute of Molecular Biology, and Institute of Biomedical Science, National Chung Cheng University, 168 University Road, Min-Hsiung, Chia-Yi, Taiwan

Received 10 June 2008; received in revised form 16 November 2008; accepted 20 August 2009.

Article Outline

Background/Purpose

Oral squamous cell carcinoma (OSCC) is an aggressive tumor and its occurrence in Taiwan is closely related to chronic smoking, alcohol consumption, and especially to betel quid chewing. It became the fourth most common malignant tumor of Taiwanese men in 2006. Unfortunately, there are few biomarkers for diagnosis and treatment of this disease.

Methods

To find potential markers, two domestic cell lines (OC2 and OCSL) derived from different grades of OSCC were established and their proteins were compared by global proteomic analysis. The expression differences of GRP78 protein in these two cell lines and clinical samples from OSCC patients were verified.

Results

Of the 11 candidate proteins expressed differentially in both cell lines, six [heat shock protein 90 kDa beta member 1 (94 kDa glucose-regulated protein; GRP94), protein disulfide-isomerase precursor, vimentin, tubulin beta-2C chain, 78 kDa glucose-regulated protein precursor (GRP78), and annexin A2] were increased in OC2 cells (low-grade OSCC), and five (heat shock protein 90-beta, annexin A1, stress-induced phosphoprotein 1, elongation factor-2, and integrin alpha-3 precursor) were increased in OCSL cells (high-grade OSCC). Some of these proteins have been previously associated with malignant tumors, but no previous association of GRP78 with OSCC has been reported. GRP78 protein expression in these two OSCC cell lines was confirmed by Western blotting. Immunohistochemical staining of clinical samples from OSCC patients revealed that decreased GRP78 protein expression was significantly correlated with advance tumor stage (p < 0.001) and neck lymph node metastasis (p = 0.001).

Conclusion

GRP78 protein is a possible biomarker of oral cancer in Taiwan.

Key Words:  GRP78 , mass spectrometry , oral neoplasms , proteomics , two dimensional gel electrophoresis

No full text is available. To read the body of this article, please view the PDF online.

 

Back to Article Outline

References 

  1. Lin YS , Jen YM , Wang BB , et al.   Epidemiology of oral cavity cancer in Taiwan with emphasis on the role of betel nut chewing . ORL J Otorhinolaryngol Relat Spec . 2005;67:230–236
  2. Department of Health Annual Statistics Information Service  . Mortality Rates for 2006 . Available at: http://www.doh.gov.tw/EN2006/DM/DM2.aspx?now_fod_list_no=9377&class_no=390&level_no=2 [Date accessed: April 29, 2010]
  3. Bureau of Health Promotion  , Department of Health, ROC  . Cancer Registry Annual Report . Available at: http://tcr.cph.ntu.edu.tw/main.php?Page=N2 2006; [Date accessed: April 29, 2010]
  4. Liaw GA , Yen CY , Chiang WF , et al.   Outcome of treatment with total main tumor resection and supraomohyoid neck dissection in oral squamous cell carcinoma . J Formos Med Assoc . 2006;105:971–977
  5. Chen PH , Shieh TY , Ho PS , et al.   Prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan . BMC Cancer . 2007;7:101
  6. He QY , Chen J , Kung HF , et al.   Identification of tumor-associated proteins in oral tongue squamous cell carcinoma by proteomics . Proteomics . 2004;4:271–278
  7. Chen J , He QY , Yuen AP , et al.   Proteomics of buccal squamous cell carcinoma: The involvement of multiple pathways in tumorigenesis . Proteomics . 2004;4:2465–2475
  8. Wong DY , Chang KW , Chen CF , et al.   Characterization of two new cell lines derived from oral cavity human squamous cell carcinomas - OC1 and OC2 . J Oral Maxillofac Surg . 1990;48:385–390
  9. Petty RD , Sutherland LA , Hunter EM , et al.   Comparison of MTT and ATP-based assays for the measurement of viable cell number . J Biolumin Chemilumin . 1995;10:29–34
  10. Veenstra TD , Yates JR . Proteomics for Biological Discovery . Hoboken, NJ: John Wiley & Sons; 2006;
  11. Matrix Science . Available at http://matrixscience.com [Date accessed: April 29, 2010]
  12. Hendershot LM . The ER function Bip is a master regulator of ER function . Mt Sinai J Med . 2004;71:289–297
  13. Rao RV , Peel A , Logvinova A , et al.   Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78 . FEBS Lett . 2002;514:122–128
  14. Uramoto H , Sugio K , Oyama T , et al.   Expression of endoplasmic reticulum molecular chaperone Grp78 in human lung cancer and its clinical significance . Lung Cancer . 2005;49:55–62
  15. Li J , Lee AS . Stress induction of Grp78/Bip and its role in cancer . Curr Mol Med . 2006;6:45–54
  16. Wang XP , Liao J , Liu GZ , et al.   Co-expression of heat shock protein 70 and glucose-regulated protein 94 in human gastric carcinoma cell line BGC-823 . World J Gastroenterol . 2005;11:3601–3604
  17. Hfaiedh N , Allagui MS , El Feki A , et al.   Effects of nickel poisoning on expression pattern of the 72/73 and 94 kDa stress proteins in rat organs and in the COS-7, HepG2, and A549 cell lines . J Biochem Mol Toxicol . 2005;19:12–18
  18. Ramakrishnan M , Schönthal AH , Lee AS . Endoplasmic reticulum stress-inducible protein GRP94 is associated with an Mg2+-dependent serine kinase activity modulated by Ca2+ and GRP78/BiP . J Cell Physiol . 1997;170:115–129
  19. Vastag B . HSP-90 inhibitors promise to complement cancer therapies . Nat Biotechnol . 2006;24:1037
  20. Lässle M , Blatch GL , Kundra V , et al.   Stress-inducible, murine protein mSTI1. Characterization of binding domains for heat shock proteins and in vitro phosphorylation by different kinases . J Biol Chem . 1997;272:1876–1884
  21. Qi YJ , He QY , Ma YF , et al.   Proteomic identification of malignant transformation-related proteins in esophageal squamous cell carcinoma . J Cell Biochem . 2008;104:1625–1635
  22. Onoue T , Uchida D , Begum NM , et al.   Epithelial-mesenchymal transition induced by the stromal cell-derived factor-1/CXCR4 system in oral squamous cell carcinoma cells . Int J Oncol . 2006;29:1133–1138
  23. Hernández-Vargas H , Rodríguez-Pinilla SM , Julián-Tendero M , et al.   Gene expression profiling of breast cancer cells in response to gemcitabine: NF-κB pathway activation as a potential mechanism of resistance . Breast Cancer Res Treat . 2007;102:157–172
  24. Raynal P , Pollard HB . Annexins. The problem of assessing the biological role for a gene family of multifunctional calcium- and phospholipids-binding proteins . Biochem Biophys Acta . 1994;1197:63–69
  25. Singh P . Role of annexin-II in GI cancers: interaction with gastrins/progastrins . Cancer Lett . 2007;252:19–35
  26. Garcia Pedrero JM , Fernandez MP , Morgan RO , et al.   Annexin A1 down-regulation in head and neck cancer is associated with epithelial differentiation status . Am J Pathol . 2004;164:73–79
  27. Lin CY , Jeng YM , Chou HY , et al.   Nuclear localization of annexin A1 is a prognostic factor in oral squamous cell carcinoma . J Surg Oncol . 2008;97:544–550
  28. Merrick WC . Mechanism and regulation of eukaryotic protein synthesis . Microbiol Mol Biol Rev . 1992;56:291–315
  29. Nystrom ML , McCulloch D , Weinreb PH , et al.   Cyclooxygenase-2 inhibition suppresses αvβ6 integrin-dependent oral squamous carcinoma invasion . Cancer Res . 2006;66:10833–10842

Back to Article Outline

Supplementary data 

    PII: S0929-6646(10)60060-5

    doi:10.1016/S0929-6646(10)60060-5

    Journal of the Formosan Medical Association
    Volume 109, Issue 5 , Pages 326-337, May 2010