53P - Iron (de)regulation in breast cancer: a role for stromal inflammatory cells in the tumor microenvironment

Date 08 May 2014
Event IMPAKT 2014
Session Welcome reception and Poster Walk
Topics Breast Cancer
Pathology/Molecular Biology
Presenter Oriana Marques
Citation Annals of Oncology (2014) 25 (suppl_1): i17-i18. 10.1093/annonc/mdu067
Authors O. Marques1, G. Porto2, A. Rêma3, F. Faria3, J.P. Pinto2, B.M. Da Silva1, C. Lopes3
  • 1Unit For Multidisciplinary Biomedical Research, Abel Salazar Institute for Biomedical Sciences, University of Porto, 4050-313 PORTO - Porto/PT
  • 2Basic And Clinical Research On Iron Biology, Institute of Molecular and Cellular Biology, 4150-180 - Porto/PT
  • 3Pathology And Molecular Immunology, Abel Salazar Institute for Biomedical Sciences, University of Porto, 4050-313 PORTO - Porto/PT

Abstract

Iron is a vital element involved in several cellular key processes. Cells acquire iron mostly by the transferrin receptor 1 (TfR1), store it in ferritin (Ft) and may export it by ferroportin (FPN1) under hepcidin (HAMP) regulation. Besides taking up iron for their own survival, circulating leukocytes are also capable of exporting iron in some conditions. We hypothesize that stromal inflammatory cells, by constituting a potential iron delivery system, may have an important role in breast cancer progression. The expression of the most relevant iron metabolism proteins (hepcidin, ferroportin, transferrin receptor 1 and ferritin-H) was assessed by immunohistochemistry in 277 tissue microarray spots from 146 samples, including 116 from mastectomy reductions, 54 from ductal carcinoma in situ (DCIS) and 107 from invasive ductal carcinoma (IDC). Representative lesions of each sample type were evaluated. Human donor liver and liver from Hamp-/- mice were used as staining controls. Breast cancer epithelial cells present an iron-gathering phenotype with higher expression of hepcidin, TfR1 and lower Ft-H than in normal mastectomy samples, which is compatible with a proliferative status. Conversely, lymphocytes and macrophages display an iron-donor phenotype with higher FPN1 and Ft-H expression which fits with the idea of an iron delivery system, while maintaining an activation profile with increased hepcidin and TfR1 expression. Preliminary data suggests that this phenotype may be particularly important during invasive transition as observed by the higher iron export potential in high grade in situ when compared with small-sized invasive lesions. Tumor size is positively correlated with TfR1 expression (R0.411, p0.005) and hormone receptor negative status with FPN1 (p