title: Autoantibody signatures involving glycolysis and splicesome proteins precede a diagnosis of breast cancer among postmenopausal women.
abstract: We assessed the autoantibody repertoire of a mouse model engineered to develop breast cancer and the repertoire of autoantibodies in human plasmas collected at a preclinical time point and at the time of clinical diagnosis of breast cancer. In seeking to identify common pathways, networks, and protein families associated with the humoral response, we elucidated the dynamic nature of tumor antigens and autoantibody interactions. Lysate proteins from an immortalized cell line from a MMTV-neu mouse model and from MCF7 human breast cancers were spotted onto nitrocellulose microarrays and hybridized with mouse and human plasma samples, respectively. Immunoglobulin-based plasma immunoreactivity against glycolysis and spliceosome proteins was a predominant feature observed both in tumor-bearing mice and in prediagnostic human samples. Interestingly, autoantibody reactivity was more pronounced further away than closer to diagnosis. We provide evidence for dynamic changes in autoantibody reactivity with tumor development and progression that may depend, in part, on the extent of antigen-antibody interactions.
authors.affiliation: Fred Hutchinson Cancer Research Center and Tumor Vaccine Group, University of Washington, Seattle, WA 98109, USA.
authors.forename: Jon J
authors.initials: JJ
authors.lastname: Ladd
authors.forename: Timothy
authors.initials: T
authors.lastname: Chao
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Johnson
authors.forename: Ji
authors.initials: J
authors.lastname: Qiu
authors.forename: Alice
authors.initials: A
authors.lastname: Chin
authors.forename: Rebecca
authors.initials: R
authors.lastname: Israel
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Pitteri
authors.forename: Jianning
authors.initials: J
authors.lastname: Mao
authors.forename: Mei
authors.initials: M
authors.lastname: Wu
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Amon
authors.forename: Martin
authors.initials: M
authors.lastname: McIntosh
authors.forename: Christopher
authors.initials: C
authors.lastname: Li
authors.forename: Ross
authors.initials: R
authors.lastname: Prentice
authors.forename: Nora
authors.initials: N
authors.lastname: Disis
authors.forename: Samir
authors.initials: S
authors.lastname: Hanash
mesh_terms: D000368:Aged; D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006019:Glycolysis / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D017698:Postmenopause; D017381:Spliceosomes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D001323:Autoantibodies