Immunological and pathobiological roles of fibulin-1 in breast cancer

Serenella M. Pupa, Scott W. Argraves, Stefania Forti, Patrizia Casalini, Valeria Berno, Roberto Agresti, Piera Aiello, Annamaria Invernizzi, Paola Baldassari, Waleed Otwal, Roberta Mortarini, Andrea Anichini, Sylvie Ménard

Research output: Contribution to journalArticlepeer-review

Abstract

Fibulin-1 (Fbln-1) is an immunogenic breast cancer-related glycoprotein identified by serological analysis of cDNA expression library (SEREX) strategy. Here, we show that dendritic cells from two breast cancer patients elicited a CD4+-mediated T-cell response to Fbln-1 presentation. In both patients, an antibody response to Fbln-1 was also found. By contrast, a Fbln-1-seronegative patient and a weakly seropositive patient demonstrated no such T-cell response. Analysis of human breast cancers for Fbln-1 RNA and protein expression revealed the presence of Fbln-1C and -1D variants. Fbln-1 was detected in the cytoplasm and at the cell surface of different human breast carcinoma cell lines. Immunohistochemical analysis of 528 archival primary breast carcinomas showed the expression of Fbln-1 in 35% of the cases. When the immunohistochemical findings were compared against pathobiological information associated with each specimen, an inverse relationship between Fbln-1 and cathepsin D expression was observed (P = 0.04). Furthermore, even though long-term survival was similar between Fbln-1-positive and -negative cases, the survival of Fbln-1-positive cases improved when a lymphoid infiltrate was present at the tumour site. Taken together, our findings of an Fbln-1-specific immunity and the improved survival associated with Fbln-1 expression in the presence of lymphoid infiltration point to a role of Fbln-1 in tumour immunosurveillance.

Original languageEnglish
Pages (from-to)2153-2160
Number of pages8
JournalOncogene
Volume23
Issue number12
DOIs
Publication statusPublished - Mar 18 2004

Keywords

  • B and T lymphocytes
  • Breast cancer
  • Fibulin-1
  • SEREX
  • Tumour antigen

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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