Immunological and pathobiological roles of fibulin-1 in breast cancer

Oncogene. 2004 Mar 18;23(12):2153-60. doi: 10.1038/sj.onc.1207323.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / metabolism
  • B-Lymphocytes / immunology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Carcinoma / genetics*
  • Carcinoma / immunology*
  • Carcinoma / pathology
  • Cathepsin D / metabolism
  • Cell Line, Tumor
  • Cytoplasm / genetics
  • Cytoplasm / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Lymphocyte Activation
  • Survival Analysis
  • T-Lymphocytes / immunology


  • Antibodies, Monoclonal
  • Calcium-Binding Proteins
  • fibulin
  • Interleukin-4
  • Interferon-gamma
  • Cathepsin D