title: Spontaneous immunogenicity of ribosomal P0 protein in patients with benign and malignant breast lesions and delay of mammary tumor growth in P0-vaccinated mice.
abstract: A common carboxyl-terminal epitope (C-22 P0) of the ribosomal P proteins (P0, P1 and P2) was shown to elicit autoantibodies in systemic lupus erythematosus (SLE) and in head and neck cancer patients. In this report we provide evidence for the in vivo immunogenicity of the P0 protein in breast cancer patients. Using recombinant P proteins, we demonstrated that sera from breast carcinoma patients (8/75) displayed significant reactivity to P0 protein when compared with healthy donor sera (0/45). Four out of the eight sera showed simultaneous reactivity to all P proteins. Breast benign tumor (3/17) and mammary hyperplasia (3/17) patient sera also showed significant reactivity to P proteins, thus suggesting that the occurrence of P protein autoantibodies might reveal mammary cell cycle dysregulation. Patient sera reacting with all P proteins recognized C-22 P0. Anti-P0 autoantibodies did not correlate with prognostic parameters of breast carcinomas. High level expression of C-22 P0 was found in mammary carcinomas compared with normal adjacent epithelium and benign lesions. To determine the antitumor activity of P0 as an immunogen, BALB-neuT transgenic mice displaying age-related breast cancer progression were vaccinated using xenogeneic P0 at the stage of mammary atypical hyperplasia. P0 vaccination significantly delayed the onset of mouse mammary tumors that overexpressed C-22 P0. Sera from P0 vaccinated mice recognized C-22 P0. Evidence for immunity to the P0 protein, its overexpression in carcinomas and its peculiar surface localization on cancer cells, along with its antitumor activity as an immunogen might be relevant for the use of P0 protein in monitoring cancer progression and in planning immunotherapeutic strategies.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Rome Sapienza, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Marzocchella
authors.forename: Valentina
authors.initials: V
authors.lastname: Sini
authors.forename: Oreste
authors.initials: O
authors.lastname: Buonomo
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
authors.forename: Laura
authors.initials: L
authors.lastname: Masuelli
authors.forename: Elena
authors.initials: E
authors.lastname: Bonanno
authors.forename: Florigio
authors.initials: F
authors.lastname: Lista
authors.forename: Mario
authors.initials: M
authors.lastname: Turriziani
authors.forename: Vittorio
authors.initials: V
authors.lastname: Manzari
authors.forename: Mario
authors.initials: M
authors.lastname: Roselli
authors.forename: Andrea
authors.initials: A
authors.lastname: Modesti
authors.forename: Roberto
authors.initials: R
authors.lastname: Bei
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001943:Breast Neoplasms / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology; D012269:Ribosomal Proteins / Q000276:immunology*; D014611:Vaccination
chemical_list: D001323:Autoantibodies; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; C054675:ribosomal protein P0; C524056:Erbb2 protein, mouse