Anti‑osteopontin autoantibodies in various types of cancer

Alsarkhi,Lamyaa Kadhim; Weber,Georg F.

doi:10.3892/or.2018.6768

Anti‑osteopontin autoantibodies in various types of cancer

Authors:
- Lamyaa Kadhim Alsarkhi
- Georg F. Weber
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Affiliations: College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH 45267‑0004, USA
Published online on: October 5, 2018 https://doi.org/10.3892/or.2018.6768
Pages: 3879-3889

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Abstract

The aberrant processing of biomolecules by cancer cells may give rise to autoimmune phenomena. The metastasis gene osteopontin is alternatively spliced only in transformed cells, and the variants promote tumor progression. They may also serve as tumor‑associated antigens, and their neutralization by autoantibodies could favorably affect prognosis. A competitive solid‑phase ELISA format was applied to determine reactivity toward recombinant osteopontin in human serum or plasma samples. Approximately 35% of thyroid cancer patients and 15% of other cancer patients were found to harbor autoantibodies directed to osteopontin variants, averaging 21% of patients across all cancers studied. The reactivity of the autoantibodies was consistent with the differential appearance of splice variants in individual malignancies. In thyroid cancer, autoantibodies were found to be more frequently associated with a milder form of the disease. The junctions of osteopontin splice variants produced by cancers represent tumor‑associated neo‑epitopes. Whereas the uniqueness of their sequences renders the acquisition of tolerance during immune maturation improbable, their immunogenicity is predicted to be low. The rare occurrence of antibodies to either osteopontin‑b or osteopontin‑c suggests that the breaking of tolerance to full‑length osteopontin is more prevalent in tumor autoimmunity than a reaction to a poorly immunogenic neo‑epitope.

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1	Senger DR, Perruzzi CA and Papadopoulos A: Elevated expression of secreted phosphoprotein I (osteopontin, 2ar) as a consequence of neoplastic transformation. Anticancer Res. 9:1291–1299. 1989.PubMed/NCBI
2	Craig AM, Smith JH and Denhardt DT: Osteopontin, a transformation-associated cell adhesion phosphoprotein, is induced by 12-O-tetradecanoylphorbol 13-acetate in mouse epidermis. J Biol Chem. 264:9682–9689. 1989.PubMed/NCBI
3	Weber GF, Lett GS and Haubein NC: Osteopontin is a marker for cancer aggressiveness and patient survival. Br J Cancer. 103:861–869. 2010. View Article : Google Scholar : PubMed/NCBI
4	Weber GF, Lett GS and Haubein NC: Categorical meta-analysis of Osteopontin as a clinical cancer marker. Oncol Rep. 25:433–441. 2011. View Article : Google Scholar : PubMed/NCBI
5	He B, Mirza M and Weber GF: An osteopontin splice variant induces anchorage independence in human breast cancer cells. Oncogene. 25:2192–2202. 2006. View Article : Google Scholar : PubMed/NCBI
6	Merl J, Deeg CA, Swadzba ME, Ueffing M and Hauck SM: Identification of autoantigens in body fluids by combining pull-downs and organic precipitations of intact immune complexes with quantitative label-free mass spectrometry. J Proteome Res. 12:5656–5665. 2013. View Article : Google Scholar : PubMed/NCBI
7	Du H, Masuko-Hongo K, Nakamura H, Xiang Y, Bao CD, Wang XD, Chen SL, Nishioka K and Kato T: The prevalence of autoantibodies against cartilage intermediate layer protein, YKL-39, osteopontin, and cyclic citrullinated peptide in patients with early-stage knee osteoarthritis: Evidence of a variety of autoimmune processes. Rheumatol Int. 26:35–41. 2005. View Article : Google Scholar : PubMed/NCBI
8	Sakata M, Tsuruha JI, Masuko-Hongo K, Nakamura H, Matsui T, Sudo A, Nishioka K and Kato T: Autoantibodies to osteopontin in patients with osteoarthritis and rheumatoid arthritis. J Rheumatol. 28:1492–1495. 2001.PubMed/NCBI
9	Fierabracci A, Biro PA, Yiangou Y, Mennuni C, Luzzago A, Ludvigsson J, Cortese R and Bottazzo GF: Osteopontin is an autoantigen of the somatostatin cells in human islets: Identification by screening random peptide libraries with sera of patients with insulin-dependent diabetes mellitus. Vaccine. 18:342–354. 1999. View Article : Google Scholar : PubMed/NCBI
10	Watanabe M, Uchida K, Nakagaki K, Kanazawa H, Trapnell BC, Hoshino Y, Kagamu H, Yoshizawa H, Keicho N, Goto H and Nakata K: Anti-cytokine autoantibodies are ubiquitous in healthy individuals. FEBS Lett. 581:2017–2021. 2007. View Article : Google Scholar : PubMed/NCBI
11	Ying X, Zhao Y, Wang JL, Zhou X, Zhao J, He CC, Guo XJ, Jin GH, Wang LJ, Zhu Q and Han SX: Serum anti-osteopontin autoantibody as a novel diagnostic and prognostic biomarker in patients with hepatocellular carcinoma. Oncol Rep. 32:1550–1556. 2014. View Article : Google Scholar : PubMed/NCBI
12	Tilli TM, Silva EA, Matos LC, Faget DV, Dias BF, Vasconcelos JS, Yokosaki Y and Gimba ER: Osteopontin is a tumor autoantigen in prostate cancer patients. Oncol Lett. 2:109–114. 2011. View Article : Google Scholar : PubMed/NCBI
13	Anborgh PH, Wilson SM, Tuck AB, Winquist E, Schmidt N, Hart R, Kon S, Maeda M, Uede T, Stitt LW and Chambers AF: New dual monoclonal ELISA for measuring plasma osteopontin as a biomarker associated with survival in prostate cancer: Clinical validation and comparison of multiple ELISAs. Clin Chem. 55:895–903. 2009. View Article : Google Scholar : PubMed/NCBI
14	Hartung F and Weber GF: RNA Blood levels of osteopontin splice variants are cancer markers. Springerplus. 2:1102013. View Article : Google Scholar : PubMed/NCBI
15	Mirza M, Shaughnessy E, Hurley JK, Vanpatten KA, Pestano GA, He B and Weber GF: Osteopontin-c is a selective marker for breast cancer. Int J Cancer. 122:889–897. 2008. View Article : Google Scholar : PubMed/NCBI
16	Yu XM, Schneider DF, Leverson G, Chen H and Sippel RS: Follicular variant of papillary thyroid carcinoma is a unique clinical entity: A population-based study of 10,740 cases. Thyroid. 23:1263–1268. 2013. View Article : Google Scholar : PubMed/NCBI
17	Ghossein R and Livolsi VA: Papillary thyroid carcinoma tall cell variant. Thyroid. 18:1179–1181. 2008. View Article : Google Scholar : PubMed/NCBI
18	Aboelnaga EM and Ahmed RA: Difference between papillary and follicular thyroid carcinoma outcomes: An experience from Egyptian institution. Cancer Biol Med. 12:53–59. 2015.PubMed/NCBI
19	Zduniak K, Agrawal A, Agrawal S, Hossain MM, Ziolkowski P and Weber GF: Osteopontin splice variants are differential predictors of breast cancer treatment responses. BMC Cancer. 16:4412016. View Article : Google Scholar : PubMed/NCBI
20	Zduniak K, Ziolkowski P, Ahlin C, Agrawal A, Agrawal S, Blomqvist C, Fjällskog ML and Weber GF: Nuclear Osteopontin-c is a prognostic breast cancer marker. Br J Cancer. 112:729–738. 2015. View Article : Google Scholar : PubMed/NCBI
21	Ashkar S, Weber GF, Panoutsakopoulou V, Sanchirico ME, Janssen M, Zawaideh S, Rittling S, Denhardt DT, Glimcher MJ and Cantor H: Eta-1 (Osteopontin): An early component of type 1 (cell-mediated) immunity. Science. 287:860–864. 2000. View Article : Google Scholar : PubMed/NCBI