Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
June 2012 Volume 3 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June 2012 Volume 3 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Autoantibodies against the signal peptide domain of Muc1 in patients with multiple myeloma: Implications for disease diagnosis and prognosis

  • Authors:
    • Riva Kovjazin
    • Anna Dubnik
    • Galit Horn
    • Nechama I. Smorodinsky
    • Izhar Hardan
    • Michael Yechiel Shapira
    • Lior Carmon
  • View Affiliations / Copyright

    Affiliations: Vaxil BioTherapeutics, Ltd., Weizmann Science Park, Nes Ziona, Israel, Department of Cell Research and Immunology, The Alec and Myra Marmot Hybridoma Unit, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel, Hematology Institute, Meir Medical Center, Kfar Saba, Israel, Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  • Pages: 1092-1098
    |
    Published online on: April 3, 2012
       https://doi.org/10.3892/etm.2012.538
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Naturally generated autoantibodies to tumor-associ­ated antigens such as MUC1 can assist in cancer diagnosis and prognosis. While previous studies have concentrated on the tandem repeat array domain of MUC1, here we focused on MUC1's signal peptide domain. We used ELISA assays with MUC1-specific epitopes and antibodies to quantify soluble MUC1 antigen and anti-MUC1 autoantibodies against the tandem repeat array and signal peptide domains in 15 naïve donors and 27 multiple myeloma cancer patients. We showed a significant increase in up to 24‑fold (P<0.004) only in the levels of anti-MUC1 signal peptide autoantibodies in the sera of multiple myeloma patients vs. naïve donors. This increase stemmed chiefly from the preferred immunogenicity of the signal peptide. Moreover, a significant positive correlation (R2=0.5361, P<0.048, Pearson correlation) was shown between the levels of soluble MUC1 and anti-MUC1 signal peptide autoantibodies in multiple myeloma patients with progressive disease while under therapy. This is an initial report on the existence of autoantibodies to a signal peptide domain in general and to the MUC1 signal peptide domain in particular in cancer patients. The autoantibodies had MUC1 rather than signal peptide specificity. The specific nature of the antigen leading to generation of these autoantibodies is still unclear because it is unlikely that the target antigen is a major histocompatibility complex-peptide complex and we could not trace soluble MUC1 signal peptide fragments in naïve donors and multiple myeloma patients. Further validation of these findings may improve diagnostic and prognostic capabilities for MUC1-positive multiple myeloma patients and potentially, patients with other MUC1-positive cancers, as well.
View Figures

Figure 1

View References

1. 

Croce MV, Isla-Larrain MT, Demichelis SO, Gori JR, Price MR and Segal-Eiras A: Tissue and serum MUC1 mucin detection in breast cancer patients. Breast Cancer Res Treat. 81:195–207. 2003. View Article : Google Scholar : PubMed/NCBI

2. 

Luminari S, Goldaniga M, Ceccherelli F, Guffanti A, Bombardieri E, Marcheselli R, et al: Prevalence and prognostic significance of sMUC-1 levels in plasma cell dyscrasias. Br J Haematol. 121:772–774. 2003. View Article : Google Scholar : PubMed/NCBI

3. 

Treon SP, Maimonis P, Bua D, Young G, Raje N, Mollick J, et al: Elevated soluble MUC1 levels and decreased anti-MUC1 antibody levels in patients with multiple myeloma. Blood. 96:3147–3153. 2000.PubMed/NCBI

4. 

Reddish MA, MacLean GD, Poppema S, Berg A and Longenecker BM: Pre-immunotherapy serum CA27.29 (MUC-1) mucin level and CD69+ lymphocytes correlate with effects of Theratope sialyl-Tn-KLH cancer vaccine in active specific immuno therapy. Cancer Immunol Immunother. 42:303–309. 1996. View Article : Google Scholar : PubMed/NCBI

5. 

Gion M, Mione R, Leon AE and Dittadi R: Comparison of the diagnostic accuracy of CA27.29 and CA15.3 in primary breast cancer. Clin Chem. 45:630–637. 1999.

6. 

Lu H, Goodell V and Disis ML: Humoral immunity directed against tumor-associated antigens as potential biomarkers for the early diagnosis of cancer. J Proteome Res. 7:1388–1394. 2008. View Article : Google Scholar : PubMed/NCBI

7. 

MacLean GD, Reddish MA, Koganty RR and Longenecker BM: Antibodies against mucin-associated sialyl-Tn epitopes correlate with survival of metastatic adenocarcinoma patients undergoing active specific immunotherapy with synthetic STn vaccine. J Immunother Emphasis Tumor Immunol. 19:59–68. 1996. View Article : Google Scholar

8. 

Brossart P, Heinrich KS, Stuhler G, Behnke L, Reichardt VL, Stevanovic S, et al: Identification of HLA-A2-restricted T-cell epitopes derived from the MUC1 tumor antigen for broadly applicable vaccine therapies. Blood. 93:4309–4317. 1999.PubMed/NCBI

9. 

Carmon L, El-Shami KM, Paz A, Pascolo S, Tzehoval E, Tirosh B, et al: Novel breast-tumor-associated MUC1-derived peptides: characterization in Db-/- x beta2 microglobulin (beta2m) null mice transgenic for a chimeric HLA-A2.1/Db-beta2 micro-globulin single chain. Int J Cancer. 85:391–397. 2000. View Article : Google Scholar

10. 

Kovjazin R, Volovitz I, Kundel Y, Rosenbaum E, Medalia G, Horn G, et al: ImMucin: a novel therapeutic vaccine with promiscuous MHC binding for the treatment of MUC1-expressing tumors. Vaccine. 29:4676–4686. 2011. View Article : Google Scholar : PubMed/NCBI

11. 

Singh H and Raghava GP: ProPred: prediction of HLA-DR binding sites. Bioinformatics. 17:1236–1237. 2001. View Article : Google Scholar : PubMed/NCBI

12. 

Vita R, Zarebski L, Greenbaum JA, Emami H, Hoof I, Salimi N, et al: The immune epitope database 2.0. Nucleic Acids Res. 38:D854–D862. 2010. View Article : Google Scholar : PubMed/NCBI

13. 

Kolaskar AS and Tongaonkar PC: A semi-empirical method for prediction of antigenic determinants on protein antigens. FEBS Lett. 276:172–174. 1990. View Article : Google Scholar : PubMed/NCBI

14. 

Horn G, Gaziel A, Wreschner DH, Smorodinsky NI and Ehrlich M: ERK and PI3K regulate different aspects of the epithelial to mesenchymal transition of mammary tumor cells induced by truncated MUC1. Exp Cell Res. 315:1490–1504. 2009. View Article : Google Scholar : PubMed/NCBI

15. 

Keydar I, Chou CS, Hareuveni M, Tsarfaty I, Sahar E, Selzer G, et al: Production and characterization of monoclonal antibodies identifying breast tumor-associated antigens. Proc Natl Acad Sci USA. 86:1362–1366. 1989. View Article : Google Scholar : PubMed/NCBI

16. 

Palmer M, Parker J, Modi S, Butts C, Smylie M, Meikle A, et al: Phase I study of the BLP25 (MUC1 peptide) liposomal vaccine for active specific immunotherapy in stage IIIB/IV non-small cell lung cancer. Clin Lung Cancer. 3:49–58. 2001. View Article : Google Scholar : PubMed/NCBI

17. 

Sangha R and North S: L-BLP25: a MUC1-targeted peptide vaccine therapy in prostate cancer. Expert Opin Biol Ther. 7:1723–1730. 2007. View Article : Google Scholar : PubMed/NCBI

18. 

Kovjazin R, Volovitz I, Daon Y, Vider-Shalit T, Azran R, Tsaban L, et al: Signal peptides and trans-membrane regions are broadly immunogenic and have high CD8+ T cell epitope densities: implications for vaccine development. Mol Immunol. 48:1009–1018. 2011. View Article : Google Scholar : PubMed/NCBI

19. 

Apostolopoulos V and McKenzie IF: Cellular mucins: targets for immunotherapy. Crit Rev Immunol. 14:293–309. 1994. View Article : Google Scholar : PubMed/NCBI

20. 

Graham RA, Burchell JM and Taylor-Papadimitriou J: The polymorphic epithelial mucin: potential as an immunogen for a cancer vaccine. Cancer Immunol Immunother. 42:71–80. 1996. View Article : Google Scholar : PubMed/NCBI

21. 

Ho SB, Niehans GA, Lyftogt C, Yan PS, Cherwitz DL, Gum ET, et al: Heterogeneity of mucin gene expression in normal and neoplastic tissues. Cancer Res. 53:641–651. 1993.PubMed/NCBI

22. 

Tang CK, Katsara M and Apostolopoulos V: Strategies used for MUC1 immunotherapy: human clinical studies. Expert Rev Vaccines. 7:963–975. 2008. View Article : Google Scholar : PubMed/NCBI

23. 

Baty D and Lazdunski C: An anti-(signal peptide) antibody: purification, properties and use as a conformational probe. Eur J Biochem. 102:503–507. 1979. View Article : Google Scholar : PubMed/NCBI

24. 

Harboe M, Whelan AO, Ulvund G, McNair J, Pollock JM, Hewinson RG, et al: Generation of antibodies to the signal peptide of the MPT83 lipoprotein of Mycobacterium tuberculosis. Scand J Immunol. 55:82–87. 2002. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kovjazin R, Dubnik A, Horn G, Smorodinsky NI, Hardan I, Shapira MY and Carmon L: Autoantibodies against the signal peptide domain of Muc1 in patients with multiple myeloma: Implications for disease diagnosis and prognosis. Exp Ther Med 3: 1092-1098, 2012.
APA
Kovjazin, R., Dubnik, A., Horn, G., Smorodinsky, N.I., Hardan, I., Shapira, M.Y., & Carmon, L. (2012). Autoantibodies against the signal peptide domain of Muc1 in patients with multiple myeloma: Implications for disease diagnosis and prognosis. Experimental and Therapeutic Medicine, 3, 1092-1098. https://doi.org/10.3892/etm.2012.538
MLA
Kovjazin, R., Dubnik, A., Horn, G., Smorodinsky, N. I., Hardan, I., Shapira, M. Y., Carmon, L."Autoantibodies against the signal peptide domain of Muc1 in patients with multiple myeloma: Implications for disease diagnosis and prognosis". Experimental and Therapeutic Medicine 3.6 (2012): 1092-1098.
Chicago
Kovjazin, R., Dubnik, A., Horn, G., Smorodinsky, N. I., Hardan, I., Shapira, M. Y., Carmon, L."Autoantibodies against the signal peptide domain of Muc1 in patients with multiple myeloma: Implications for disease diagnosis and prognosis". Experimental and Therapeutic Medicine 3, no. 6 (2012): 1092-1098. https://doi.org/10.3892/etm.2012.538
Copy and paste a formatted citation
x
Spandidos Publications style
Kovjazin R, Dubnik A, Horn G, Smorodinsky NI, Hardan I, Shapira MY and Carmon L: Autoantibodies against the signal peptide domain of Muc1 in patients with multiple myeloma: Implications for disease diagnosis and prognosis. Exp Ther Med 3: 1092-1098, 2012.
APA
Kovjazin, R., Dubnik, A., Horn, G., Smorodinsky, N.I., Hardan, I., Shapira, M.Y., & Carmon, L. (2012). Autoantibodies against the signal peptide domain of Muc1 in patients with multiple myeloma: Implications for disease diagnosis and prognosis. Experimental and Therapeutic Medicine, 3, 1092-1098. https://doi.org/10.3892/etm.2012.538
MLA
Kovjazin, R., Dubnik, A., Horn, G., Smorodinsky, N. I., Hardan, I., Shapira, M. Y., Carmon, L."Autoantibodies against the signal peptide domain of Muc1 in patients with multiple myeloma: Implications for disease diagnosis and prognosis". Experimental and Therapeutic Medicine 3.6 (2012): 1092-1098.
Chicago
Kovjazin, R., Dubnik, A., Horn, G., Smorodinsky, N. I., Hardan, I., Shapira, M. Y., Carmon, L."Autoantibodies against the signal peptide domain of Muc1 in patients with multiple myeloma: Implications for disease diagnosis and prognosis". Experimental and Therapeutic Medicine 3, no. 6 (2012): 1092-1098. https://doi.org/10.3892/etm.2012.538
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team