Cited by 215Iron Metabolism and DisordersFerroptosis and cancer prognosisErythropoietin and Anemia Treatment

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The iron metabolism of neoplastic cells: alterations that facilitate proliferation?

Kwok, Juliana C, Richardson, Des R.·2002·Critical Reviews in Oncology/Hematology

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Abstract

For many years it has been known that neoplastic cells express high levels of the transferrin receptor 1 (TfR1) and internalize iron (Fe) from transferrin (Tf) at a tremendous rate. Considering the high requirement of neoplastic cells for Fe, understanding its metabolism is vital in terms of devising potential new therapies. Apart from TfR1, a number of molecules have been identified that may have roles in Fe metabolism and cellular proliferation. These molecules include transferrin (Tf), the oestrogen-inducible transferrin receptor-like protein, transferrin receptor 2 (TfR2), melanotransferrin (MTf), ceruloplasmin, and ferritin. In the present review these latter molecules are discussed in terms of their potential functions in tumour cell Fe metabolism and proliferation. Further studies are essential to determine the specific roles of these proteins in the pathogenesis of cancer.

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Mitoxantrone-Loaded Nanoferritin Slows Tumor Growth and Improves the Overall Survival Rate in a Subcutaneous Pancreatic Cancer Mouse Model
Conti, G., Pitea, M., Ossanna, R., Opri, R., Tisci, G., Falvo, E., Innamorati, G., Ghanem, E., Sbarbati, A., Ceci, P., et al. (2021) · Biomedicines · doi:10.3390/biomedicines9111622 · Cited by 7
“The tumorigenicity associated with the expression of TfR is not only due to the greater demand for iron, an essential cofactor for the functionality of many enzymes including those involved in the synthesis of nucleic acids feeding cellular proliferation, but also to other factors [24,25].”
Background
MDM2 SNP309 genotype is associated with ferritin and LDH serum levels in children with stage 4 neuroblastoma
Parodi, S., Perfumo, C., Garaventa, A., Inga, A., Mazzocco, K., Defferrari, R., Tonini, G. P., Fronza, G., & Haupt, R. (2010) · Pediatric Blood & Cancer · doi:10.1002/pbc.22477 · Cited by 6
“Iron metabolism in NB is altered compared to other cell types and cells from NB have been reported to contain iron-rich ferritin and to secrete it [28].”
Background
Role of Immune Microenvironmental Factors for Improving the IPI-related Risk Stratification of Aggressive B Cell Lymphoma.
Gong, Y., Chen, R., Zhang, X., Zou, Z., & Chen, X. H. (2017) · PubMed · doi:10.3967/bes2017.065 · Cited by 6
“In addition, the components of the differential white blood cell count (WBC-DC), systematic inflammatory and metabolic markers, such as LDH, β2-microglobulin (β2MG), and iron, in peripheral blood are useful inexpensive parameters to categorize the prognoses of malignant diseases including solid and hematological malig…”
Background
Engineering Quantum Dot (Cadmium Sulfide) on Antibodies for Fluoroimmunoassays
Lodhi, M. S., & Samra, Z. Q. (2020) · Journal of Nanomaterials · doi:10.1155/2020/4707123 · Cited by 6
“That can be justified due to high iron demand of abruptly growing cells for their DNA manipulation and energy cycles involved in cell cycle progression [23, 24].”
Background
A systematic review and meta-analysis on the association of serum and tumor tissue iron and risk of breast cancer.
Sanagoo, A., Kiani, F., Naz, M. S. G., Sayehmiri, F., Koohi, F., Jouybari, L. M., & Dousti, M. (2020) · Europe PMC (PubMed Central) · doi:10.22088/cjim.11.1.1 · Cited by 6
“It fundamentally contributes in the arrangement of cellular growth and differentiation (46).”
Background
Iron metabolism in prostate cancer
Koltai, T., Reshkin, S. J., Baltazar, F., & Fliegel, L. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-90528-2.00011-4 · Cited by 5
The Antimalarial Drug Artesunate Mediates Selective Cytotoxicity by Upregulating HO-1 in Melanoma Cells
Jochims, F., Strohm, R., von Montfort, C., Wenzel, C.-K., Klahm, N. P., Kondadi, A. K., Stahl, W., Reichert, A. S., & Brenneisen, P. (2023) · Biomedicines · doi:10.3390/biomedicines11092393 · Cited by 5
The cell-permeable iron chelator M606 inhibits MYCN-driven neuroblastoma via an E2F3-mediated response
Pandher, R., Xue, C., Gamble, L. D., Milazzo, G., Giacomo, S. D., Murray, J. E., Cheung, L., Ferrucci, F., Palombo, M., Purgato, S., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2420011122 · Cited by 5
“Despite iron being an essential element required for normal cell proliferation and metabolism, altered iron metabolism has been implicated in tumor initiation and growth ( 38 , 39 ).”
Ascorbate and Tumor Cell Iron Metabolism: The Evolving Story and Its Link to Pathology
Bae, D.-H., Azad, M. G., Kalinowski, D. S., Lane, D. J. R., Jansson, P. J., & Richardson, D. R. (2019) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7903 · Cited by 6
“Iron plays a fundamental role in cellular survival and proliferation (114, 128).”
Cancer and mosquitoes – An unsuspected close connection
Arnal, A., Roche, B., Gouagna, L., Dujon, A. M., Újvári, B., Corbel, V., Remoué, F., Poinsignon, A., Pompon, J., Giraudeau, M., et al. (2020) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2020.140631 · Cited by 5
Magnetospirillum magneticum triggers apoptotic pathways in human breast cancer cells
Menghini, S., Vizovišek, M., Enders, J., & Schuerle, S. (2023) · Cancer & Metabolism · doi:10.1186/s40170-023-00313-3 · Cited by 6
A comparative study of the iron status of patients with oesophageal adenocarcinoma to determine suitability for a clinical trial of iron chelation therapy
Ford, S., Bedford, M., Pang, W.-Y., WOOD, A. G., Iqbal, T. H., Tselepis, C., & Tucker, O. (2014) · Annals of The Royal College of Surgeons of England · doi:10.1308/003588414x13946184900282 · Cited by 6
“These associations are not entirely surprising as iron is essential for a number of key cellular processes including synthesis of deoxyribonucleic acid, adenosine triphosphate generation and cell cycle progression, all of which are increased in cancer.(10) With this in mind, there is now evidence suggesting that iron…”
Background
Iron uptake by melanoma cells from the soluble form of the transferrin homologue, melanotransferrin
Food, M. R., & Richardson, D. R. (2002) · Redox Report · doi:10.1179/135100002125000794 · Cited by 5
Unlocking the potential of melanotransferrin (CD228): implications for targeted drug development and novel therapeutic avenues
Zhang, Y., Song, D., Han, X., Liu, H., Wang, Y., Wang, X., & Dou, C. (2024) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2024.2441705 · Cited by 5
“Researchers initially hypothesized that the overexpression of CD228 in melanoma cells satisfies the iron requirements for tumor proliferation [12,13].”
YM155, specific survivin inhibitor, can enhance artesunate-induced cytotoxicity in HCT116 colon cancer cells
Kim, E. T., & Park, D.-G. (2020) · Korean Journal of Clinical Oncology · doi:10.14216/kjco.20020 · Cited by 4
“Cancer cells contain substantial free iron, resulting from their higher rate of iron uptake via transferrin receptors compared with normal cells [5].”
Background
Changes in Serum Iron, Total Iron Binding Capacity and Transferrin Saturation Percent in Sudanese Females Newly Diagnosed with Breast Cancer at Khartoum Oncology Hospital: A case- control study
Mustafa, R. M. A., & Husain, N. E. (2017) · Sudan Journal of Medical Sciences · doi:10.18502/sjms.v12i3.915 · Cited by 4
“Being highly proliferative, tumour cells need more iron and they usually show high intracellular iron concentration [13, 14].”
Background
Quilamine HQ1-44, an iron chelator vectorized toward tumor cells by the polyamine transport system, inhibits HCT116 tumor growth without adverse effect
Renaud, S., Corcé, V., Cannie, I., Ropert, M., Lepage, S., Loréal, O., Deniaud, D., & Gaboriau, F. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.06.001 · Cited by 4
“the iron importing proteins and a decrease in the expression of iron exporting proteins [4-6].”
Background
Synthesis of some benzylidene thiosemicarbazide derivatives and evaluation of their cytotoxicity on U87, MCF-7, A549, 3T3 and HUVEC cell lines
Eslaminejad, T., Pourshojaei, Y., Naghizadeh, M., Eslami, H., Daneshpajouh, M., & Hassanzadeh, A. (2022) · Journal of the Serbian Chemical Society · doi:10.2298/jsc210630016e · Cited by 3
Erythrophagocytosis Enhances Heme-Dependent Cytotoxicity of Antimalarial Drugs in Canine Histiocytic Sarcoma Cell Line DH82
Chikazawa, S., KITAHARA, Y., Ando, E., Hori, Y., Hoshi, F., Kanai, K., Ito, N., & Higuchi, S. (2013) · Journal of Veterinary Medical Science · doi:10.1292/jvms.13-0319 · Cited by 3
“Cancer cells have an increased capacity to synthesize heme and increased requirements for iron in order to sustain rapid cell proliferation, and this is the basis for photodynamic therapies for cancer [9, 11].”
Background
Implementing the design cues of dissociation dynamics and transmetalation in gallium( iii ) complexes to promote the anti-proliferative activity of ligands targeting intracellular iron( ii ) trafficking
Dharmasivam, M., Faiz, S., Kaya, B., Wijesinghe, T. P., Süleymanoğlu, M., Azad, M. G., Richardson, V., Zahoor, A. F., Kalinowski, D. S., Lewis, W., et al. (2026) · Chemical Science · doi:10.1039/d5sc06084b · Cited by 3
Nutrigenomics in the management and prevention of cancer
Lim, C. J. C., Lim, P. P., Pizarro, R. R. M., Segocio, H. G. B., & Ratta, K. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-824412-8.00002-3 · Cited by 3
Comparative Analysis of Iron Metabolism and Its Adjustment Changes at Cancer Patients in Childhood
Yavuz, G., Ünal, E., Taçyıldız, N., Köse, S. K., Gökçe, H., Gördü, Z., Pekpak, E., Aksoy, B. A., İlarslan, N. E. Ç., Günay, F., et al. (2017) · Iranian Journal of Pediatrics · doi:10.5812/ijp.10092 · Cited by 2
“These cancers include lung cancer, breast cancer, prostate cancer, colorectal cancer, hepatocellular cancer, pancreatic cancer, hematological cancers, renal cell carcinoma and melanoma (9).”
Background
Synthesis of a Novel Polymer- Iron (ΙΙΙ) Complex and Study of Its Anticancer Properties on A375 Melanoma Cell LinePreprint
Neisi, E., & Hasanvandi, S. (2023) · Preprints.org · doi:10.20944/preprints202308.2171.v1 · Cited by 1
A role for deferasirox as an anti-neoplastic and chemosensitising agent in gastrointestinal cancer
Bedford, M. (2015) · University of Birmingham Institutional Research Archive (University of Birmingham) · Cited by 1
Exogenously Induced Endogenous Photosensitizers
Heuck, G., & Lange, N. (2011) · Springer eBooks · doi:10.1007/978-90-481-3872-2_8
The role of haem transport and iron chelation in oesophageal cancer
Ford, S. (2013) · University of Birmingham Institutional Research Archive (University of Birmingham)
Wybrane parametry laboratoryjne w monitorowaniu chorych immunizowanych genetycznie modyfikowaną szczepionką przeciwczerniakową
Leporowska, E. (2012) · Zeszyty Naukowe WCO Letters in Oncology Science · doi:10.1016/s1734-0489(12)70007-x
Integrative Physician's Perspective, With a Special Consideration of St John’s Wort
Block, K. I. (2005) · Integrative Cancer Therapies · doi:10.1177/1534735405279877
Defining the chemical and molecular mechanisms of cytotoxicity Induced by the endoperoxide class of antimalarials
Firman, J. W. (2015) · University of Liverpool · doi:10.17638/02012740
The Diagnostic Challenge of Therapy-Related Pure Erythroid Leukemia Arising in the Setting of Multiple Myeloma
Evans, H. L. (2014) · Journal of Leukemia · doi:10.4172/2329-6917.1000141
“One caveat in solely relying on CD71 as an erythroid marker is that it can also be expressed by some other highly proliferative neoplasms such as diffuse large B-cell lymphoma [23-25], in particular, by flow cytometry phenotyping.”
Background
Iron Excess and Cancer
Davis, C. F., & Dorak, M. T. (2010) · Springer eBooks · doi:10.1007/978-1-4419-6752-7_17
“, 1988; de Sousa, 1989; Brock and Mulero, 2000; Walker and Walker, 2000; Porto and De Sousa, 2007) – Iron as an essential nutrient for proliferating neoplastic cells (Bergeron, 1986; Cazzola et al., 1990; Sussman, 1992; Kwok and Richardson, 2002; Butterworth, 2006) – Animal experiments showing pro-carcinogenic effect…”
Background
Are Calcium Channels More Important Than Calcium Influx for Cell Proliferation?
Borowiec, A., Bidaux, G., & Capiod, T. (2013) · Springer eBooks · doi:10.1007/978-94-007-6211-4_4
The cellular and functional role of melanotransferrin in melanomas
Tian, M. (2010) · cIRcle (University of British Columbia) · doi:10.14288/1.0069952
ART for Antitumor
Zeng, Q.-P. (2015) · Springer briefs in molecular science · doi:10.1007/978-3-662-47688-8_3
Ferritin Expression in Breast Cancer Infiltrating Lymphocytes. Evaluation of Biological Significance and Modulation by HLA-A*03 and HFE
Leite, L. R. (2015) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.34626/v3x7-ys11
Antitumor effect of steroidal tetraoxanes on malignantly transformed human cell lines
Žižak, Ž. S. (2012) · doi:10.2298/bg20121227zizak
Melanoma and Oxidative Stress
Armani, A. L. C., Prado, S. B. R., & Malachias, V. T. (2014) · CRC Press eBooks · doi:10.1201/b16653-31
The human neuraminidase enzyme, NEU3, regulates integrin-mediated cell migration via changes in glycolipid composition
Jia, F. (2013) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3fj29n0d
Formulation and Evaluation of Some in Vitro and in Vivo Properties of Artemether-Loaded Self Emulsifying Drug Delivery System
Ugwu, C. E. (2017)
Identification of Iron Metabolism-Related Gene Signatures for Predicting the Prognosis of Patients with Skin Cutaneous MelanomaPreprint
Guo, Y., Song, C., Zhang, L., Han, Z., & Zhu, L. (2022) · Research Square · doi:10.21203/rs.3.rs-2317277/v1

Authors: Kwok, J. C., & Richardson, D. R.
Affiliations: The Heart Research Institute (AU)
Corresponding author: Richardson, Des R.
ORCID: Richardson, Des R.
Venue: Critical Reviews in Oncology/Hematology
Publisher: Elsevier BV
Published: 2002-04
Volume: 42
Issue: 1
Pages: 65-78
ISSN: 1040-8428 (ISSN-L)
DOI: 10.1016/s1040-8428(01)00213-x
OpenAlex: W2049332203
Cited by: 215
References: 162
Citations by year: 2026: 2 · 2025: 1 · 2024: 14 · 2023: 15 · 2022: 5 · 2021: 11 · 2020: 10 · 2019: 8 · 2018: 6 · 2017: 13 · 2016: 9 · 2015: 13 · 2014: 10 · 2013: 18 · 2012: 9
FWCI: 1.04
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Critical Reviews in Oncology/Hematology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
Keywords: iron metabolism, neoplastic cells, transferrin receptor 1, transferrin receptor 2, transferrin, melanotransferrin, ceruloplasmin, ferritin, tumor cell proliferation, carcinogenesis, iron transport
MeSH terms: Animals, Antigens, Neoplasm, Biological Transport, Cell Division, Ceruloplasmin, Endocytosis, Estrogens, Ferritins, Humans, Iron, Neoplasm Proteins, Neoplasms, Receptors, Transferrin, Transferrin, Nonheme Iron Proteins, Melanoma-Specific Antigens

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The iron metabolism of neoplastic cells: alterations that facilitate proliferation?

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