Human Mena protein, a serex-defined antigen overexpressed in breast cancer eliciting both humoral and CD8+ T-cell immune response

Francesca Di Modugno, Giovanna Bronzi, Matthew J. Scanlan, Duilia Del Bello, Simona Cascioli, Irene Venturo, Claudio Botti, Maria Rita Nicotra, Marcella Mottolese, Pier Giorgio Natali, Angela Santoni, Elke Jager, Paola Nisticò

Research output: Contribution to journalArticlepeer-review

Abstract

Screening of a cDNA expression library from a primary breast tumor with the autologous patient serum led to the isolation of 6 cDNA clones corresponding to 3 different genes, including a novel gene that maps to chromosome I and encodes the human homologue of mouse Mena (hMena, cDNA clone RMNY-BR-55), a protein of the Ena/VASP family involved in the regulation of cell motility and adhesion. A cancer-restricted antibody response against hMena was demonstrated, since 18/93 cancer patient sera, the majority (10/52) from breast cancer, showed anti-hMena-specific IgG, while no antibodies were present in healthy donors. When hMena protein expression was analyzed by Western blot and immunohistochemistry, the antigen was overexpressed in the majority of breast cancer cell lines and in 75% of primary breast tumor lesions evaluated. Furthermore, when HLA-A2-restricted peptides from the hMena sequence were used to stimulate CD8+ T cells, an hMena-specific response was found in 9 out of 12 HLA-A2+ breast cancer patients. In 4 patients, this cell-mediated immune response was concomitant with antibody response to hMena. Furthermore, an hMena-specific T-cell line was established from an HLA-A2 + breast cancer patient whose primary tumor lesion overexpressed the hMena protein. The present findings highlight the emerging role that overexpression of cytoskeleton regulatory components may have in the induction of a specific antitumor immune response.

Original languageEnglish
Pages (from-to)909-918
Number of pages10
JournalInternational Journal of Cancer
Volume109
Issue number6
DOIs
Publication statusPublished - May 10 2004

Keywords

  • Cytotoxic T lymphocyte
  • Major histocompatibility complex
  • Tumor immunity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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