A link between premenopausal iron deficiency and breast cancer malignancy
Open accessAbstract
Background: Young breast cancer (BC) patients less than 45 years old are at higher risk of dying from the disease when compared to their older counterparts. However, specific risk factors leading to this poorer outcome have not been identified. Methods: One candidate is iron deficiency, as this is common in young women and a clinical feature of young age. In the present study, we used immuno-competent and immuno-deficient mouse xenograft models as well as hemoglobin as a marker of iron status in young BC patients to demonstrate whether host iron deficiency plays a pro-metastatic role. Results: We showed that mice fed an iron-deficient diet had significantly higher tumor volumes and lung metastasis compared to those fed normal iron diets. Iron deficiency mainly altered Notch but not TGF-β and Wnt signaling in the primary tumor, leading to the activation of epithelial mesenchymal transition (EMT). This was revealed by increased expression of Snai1 and decreased expression of E-cadherin. Importantly, correcting iron deficiency by iron therapy reduced primary tumor volume, lung metastasis, and reversed EMT markers in mice. Furthermore, we found that mild iron deficiency was significantly associated with lymph node invasion in young BC patients (p<0.002). Conclusions: Together, our finding indicates that host iron deficiency could be a contributor of poor prognosis in young BC patients.
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Mice fed a low-iron diet prior to implanting tumor cells showed significantly delayed tumor growth.
“Mice fed a low-iron diet prior to implanting tumor cells showed significantly delayed tumor growth [22].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [22]
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- Authors
- Jian, J., Yang, Q., Shao, Y., Axelrod, D., Smith, J., Singh, B., Krauter, S., Chiriboga, L., Yang, Z., Li, J., & Huang, X.
- Affiliations
- New York University (US)
- Tang Du Hospital (CN)
- Corresponding author
- Huang, Xi
- ORCID
- Venue
- BMC Cancer
- Published
- 2013-06-24
- Volume
- 13
- Issue
- 1
- Pages
- 307-307
- ISSN
- 1471-2407 (ISSN-L)
- PMC
- PMC3716572
- OpenAlex
- W2143033717
- Cited by
- 37
- References
- 36
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 5
- FWCI
- 1.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Cancer (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (ES00260.)
- National Cancer Institute (CA 34588, R01CA034588, CA16087, R21CA132684, P30CA016087, 5P30CA0016087-33)
- National Institute of Environmental Health Sciences (ES00260, P30ES000260)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- breast cancer, iron deficiency, premenopausal women, young age, lung metastasis, lymph node invasion, epithelial-mesenchymal transition, Notch signaling, SNAI1, E-cadherin, iron therapy, cancer prognosis
- MeSH terms
- Iron Deficiencies, Animals, Breast Neoplasms, Disease Models, Animal, Female, Fluorescent Antibody Technique, Humans, Immunohistochemistry, Mice, Inbred BALB C, Transplantation, Heterologous, Blotting, Western, Polymerase Chain Reaction, Premenopause, Mice, Epithelial-Mesenchymal Transition
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