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Anti-centrosome antibodies in breast cancer are the expression of autoimmunity

  • PATHOGENESIS AND THERAPY IN AUTOIMMUNE DISEASES
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Abstract

Centrosome abnormalities have been observed in nearly all human solid tumors, but their role in tumorigenesis is unclear. We have demonstrated that autoantibodies reacting with antigens in centrosomes are frequently found in BC sera. In this work, we attempted to characterize the centrosome antigens associated with BC. We immunoscreened a T7 cDNA library of BC proteins with BC sera, and the autoantigens identified were printed as a microarray and hybridized with BC and control sera. We used immunohistochemistry (IHC) to investigate the expression of the cloned autoantigens in BC tissue. Immunoscreening with BC sera led to the cloning of autoantibodies recognizing epitopes developing in a family of proteins located on centrosomes such as peri-centriolar material-1, isomorph CRA, stathmin1, HS actin gamma1, SUMO/sentrin peptidase 2, and ubiquitin-conjugating enzyme E2 variant 1. Antibody reactivity to these proteins that are associated with centrosome assembly and/or microtubule function was highly associated with the diagnosis of BC. IHC staining of formalin-fixed paraffin-embedded sections with specific antibodies showed that aurora and stathmin are expressed in BC. The discovery of autoantibodies to important centrosome antigens associated with BC suggests that this immune reactivity could be related to autoimmunity developing in BC. Our finding that some of these antibodies are also present in a group of healthy women suggests that breakdown of tolerance to centrosome proteins may occur early in breast carcinogenesis and that autoantibodies to centrosome antigens might be biomarkers of early BC.

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Acknowledgments

This work was done with the partial support of NIH NCI R01 122277. We thank the technical work of Naimei Tang and Xinbo Zhang in several aspects of this project.

Conflict of interest

None.

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Author notes

  1. Azadeh Stark

    Present address: Center for Clinical Epidemiology and Biostatistics, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Wayne State University School of Medicine, 540 Canfield, Detroit, MI, 48201, USA

    Marie-Claire Maroun & Félix Fernández Madrid

  2. Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, 37 Convent Dr. MSC 4255, Bldg 37 Rm 4032, Bethesda, MD, 20892-4255, USA

    Ofelia Olivero

  3. Center for Molecular Medicine and Genetics, Wayne State University, 540 E. Canfield St. 3228 Scott Hall, Detroit, MI, 48201-1928, USA

    Leonard Lipovich & Félix Fernández Madrid

  4. Department of Pathology, Henry Ford Health System, Detroit, MI, 48202, USA

    Azadeh Stark

  5. Karmanos Cancer Institute, 4100 John R Street, Detroit, MI, 48201, USA

    Larry Tait & Félix Fernández Madrid

  6. Department of Pathology, Wayne State University, Detroit, MI, USA

    Sudeshna Bandyopadhyay

  7. Department of Diagnostic Radiology, Henry Ford Hospital and Health Network, 2799 West Grand Boulevard, Detroit, MI, 48202, USA

    Matthew Burke

  8. Pathology and Laboratory Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI, 48202, USA

    Richard Zarbo & Dhananjay Chitale

  9. Department of Surgery, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI, 48202, USA

    S. David Nathanson

  10. Department of Pathology, Children’s Hospital of Michigan, Wayne State School of Medicine, Detroit, MI, USA

    Mike Long

  11. INOVA Diagnostics Inc., 9900 Old Grove Rd, San Diego, CA, 92131, USA

    Carol Peebles

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  1. Marie-Claire Maroun
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Correspondence to Marie-Claire Maroun.

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Maroun, MC., Olivero, O., Lipovich, L. et al. Anti-centrosome antibodies in breast cancer are the expression of autoimmunity. Immunol Res 60, 339–347 (2014). https://doi.org/10.1007/s12026-014-8582-4

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