Anti-osteopontin autoantibodies in various types of cancer

摘要

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.