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HFE Variants and the Expression of Iron-Related Proteins in Breast Cancer-Associated Lymphocytes and Macrophages

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  • Published:
Cancer Microenvironment

Abstract

The association of HFE (High Iron FE) major variants with breast cancer risk and behavior has been a matter of discussion for a long time. However, their impact on the expression of iron-related proteins in the breast cancer tissue has never been addressed. In the present study, hepcidin, ferroportin 1, transferrin receptor 1 (TfR1), and ferritin expressions, as well as tissue iron deposition were evaluated in a collection of samples from breast cancers patients and analyzed according to the patients’ HFE genotype. Within the group of patients with invasive carcinoma, those carrying the p.Cys282Tyr variant in heterozygosity presented a higher expression of hepcidin in lymphocytes and macrophages than wild-type or p.His63Asp carriers. An increased expression of TfR1 was also observed in all the cell types analyzed but only in p.Cys282Tyr/p.His63Asp compound heterozygous patients. A differential impact of the two HFE variants was further noticed with the observation of a significantly higher percentage of p.Cys282Tyr heterozygous patients presenting tissue iron deposition in comparison to p.His63Asp heterozygous. In the present cohort, no significant associations were found between HFE variants and classical clinicopathological markers of breast cancer behavior and prognosis. Although limited by a low sampling size, our results provide a new possible explanation for the previously reported impact of HFE major variants on breast cancer progression, i.e., not by influencing systemic iron homeostasis but rather by differentially modulating the local cellular expression of iron-related proteins and tissue iron deposition.

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Acknowledgements

OM is a recipient of the PhD grant SFRH/BD/2011/78184 from Fundação para a Ciência e Tecnologia (FCT). The authors also acknowledge financial support from ICBAS/AI&NS-UMIB and by national funds through FCT and Ministério da Educação e Ciência (MEC) and when applicable co-funded by FEDER funds within the partnership agreement PT2020 related with the research unit number 4293. The authors would like to thank Drs. Bárbara Leal, Cláudia Carvalho and Luis Cirnes for critical advice in technical procedures.

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Authors and Affiliations

  1. Unit for Multidisciplinary Biomedical Research (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal

    Oriana Marques & Berta Martins da Silva

  2. Lab Immunogenetics & Autoimmu and NeuroScien, UMIB, ICBAS, University of Porto, Porto, Portugal

    Oriana Marques

  3. Pathology and Molecular Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal

    Oriana Marques, Ana Rosa, Luciana Leite, Alexandra Rêma, Berta Martins da Silva, Graça Porto & Carlos Lopes

  4. Basic and Clinical Research on Iron Biology, Molecular and Cell Biology Institute (IBMC), University of Porto, Porto, Portugal

    Oriana Marques, Ana Rosa & Graça Porto

  5. Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal

    Oriana Marques, Ana Rosa & Graça Porto

  6. Human Genetics Department, National Institute of Health Dr. Ricardo Jorge, Lisbon, Portugal

    Paula Faustino

  7. Institute of Environmental Health, Faculty of Medicine, University of Lisbon, Lisbon, Portugal

    Paula Faustino

  8. Hematology Service, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal

    Graça Porto

  9. Department of Pathology, Portuguese Oncology Institute (IPO), Porto, Portugal

    Carlos Lopes

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  1. Oriana Marques
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  2. Ana Rosa
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  3. Luciana Leite
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  4. Paula Faustino
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  8. Carlos Lopes
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Correspondence to Oriana Marques.

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This study was approved by Centro Hospitalar do Porto Research Ethics Health Committee (228-CES) and by Centro Hospitalar do Porto Department of Education, Development and Research (152-DEFI) ethical boards. For this type of study, informed consent is not required.

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The authors declare they have no competing interests.

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Marques, O., Rosa, A., Leite, L. et al. HFE Variants and the Expression of Iron-Related Proteins in Breast Cancer-Associated Lymphocytes and Macrophages. Cancer Microenvironment 9, 85–91 (2016). https://doi.org/10.1007/s12307-016-0191-4

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  • DOI: https://doi.org/10.1007/s12307-016-0191-4

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