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Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis. Iron deficiency and angiogenesis

BACKGROUND: Young women diagnosed with breast cancer are known to have a higher mortality rate from the disease than older patients. Specific risk factors leading to this poorer outcome have not been identified. In the present study, we hypothesized that iron deficiency, a common ailment in young wo...

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Autores principales: Eckard, Jonathan, Dai, Jisen, Wu, Jing, Jian, Jinlong, Yang, Qing, Chen, Haobin, Costa, Max, Frenkel, Krystyna, Huang, Xi
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936284/
https://www.ncbi.nlm.nih.gov/pubmed/20723262
http://dx.doi.org/10.1186/1475-2867-10-28
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author Eckard, Jonathan
Dai, Jisen
Wu, Jing
Jian, Jinlong
Yang, Qing
Chen, Haobin
Costa, Max
Frenkel, Krystyna
Huang, Xi
author_facet Eckard, Jonathan
Dai, Jisen
Wu, Jing
Jian, Jinlong
Yang, Qing
Chen, Haobin
Costa, Max
Frenkel, Krystyna
Huang, Xi
author_sort Eckard, Jonathan
collection PubMed
description BACKGROUND: Young women diagnosed with breast cancer are known to have a higher mortality rate from the disease than older patients. Specific risk factors leading to this poorer outcome have not been identified. In the present study, we hypothesized that iron deficiency, a common ailment in young women, contributes to the poor outcome by promoting the hypoxia inducible factor-1α (HIF-1α and vascular endothelial growth factor (VEGF) formation. This hypothesis was tested in an in vitro cell culture model system. RESULTS: Human breast cancer MDA-MB-231 cells were transfected with transferrin receptor-1 (TfR1) shRNA to constitutively impair iron uptake. Cellular iron status was determined by a set of iron proteins and angiogenesis was evaluated by levels of VEGF in cells as well as by a mouse xenograft model. Significant decreases in ferritin with concomitant increases in VEGF were observed in TfR1 knockdown MDA-MB-231 cells when compared to the parental cells. TfR1 shRNA transfectants also evoked a stronger angiogenic response after the cells were injected subcutaneously into nude mice. The molecular mechanism appears that cellular iron deficiency elevates VEGF formation by stabilizing HIF-1α. This mechanism is also true in human breast cancer MCF-7 and liver cancer HepG2 cells. CONCLUSIONS: Cellular iron deficiency increased HIF-1α, VEGF, and angiogenesis, suggesting that systemic iron deficiency might play an important part in the tumor angiogenesis and recurrence in this young age group of breast cancer patients.
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spelling pubmed-29362842010-09-10 Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis. Iron deficiency and angiogenesis Eckard, Jonathan Dai, Jisen Wu, Jing Jian, Jinlong Yang, Qing Chen, Haobin Costa, Max Frenkel, Krystyna Huang, Xi Cancer Cell Int Primary Research BACKGROUND: Young women diagnosed with breast cancer are known to have a higher mortality rate from the disease than older patients. Specific risk factors leading to this poorer outcome have not been identified. In the present study, we hypothesized that iron deficiency, a common ailment in young women, contributes to the poor outcome by promoting the hypoxia inducible factor-1α (HIF-1α and vascular endothelial growth factor (VEGF) formation. This hypothesis was tested in an in vitro cell culture model system. RESULTS: Human breast cancer MDA-MB-231 cells were transfected with transferrin receptor-1 (TfR1) shRNA to constitutively impair iron uptake. Cellular iron status was determined by a set of iron proteins and angiogenesis was evaluated by levels of VEGF in cells as well as by a mouse xenograft model. Significant decreases in ferritin with concomitant increases in VEGF were observed in TfR1 knockdown MDA-MB-231 cells when compared to the parental cells. TfR1 shRNA transfectants also evoked a stronger angiogenic response after the cells were injected subcutaneously into nude mice. The molecular mechanism appears that cellular iron deficiency elevates VEGF formation by stabilizing HIF-1α. This mechanism is also true in human breast cancer MCF-7 and liver cancer HepG2 cells. CONCLUSIONS: Cellular iron deficiency increased HIF-1α, VEGF, and angiogenesis, suggesting that systemic iron deficiency might play an important part in the tumor angiogenesis and recurrence in this young age group of breast cancer patients. BioMed Central 2010-08-19 /pmc/articles/PMC2936284/ /pubmed/20723262 http://dx.doi.org/10.1186/1475-2867-10-28 Text en Copyright ©2010 Eckard et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Primary Research
Eckard, Jonathan
Dai, Jisen
Wu, Jing
Jian, Jinlong
Yang, Qing
Chen, Haobin
Costa, Max
Frenkel, Krystyna
Huang, Xi
Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis. Iron deficiency and angiogenesis
title Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis. Iron deficiency and angiogenesis
title_full Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis. Iron deficiency and angiogenesis
title_fullStr Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis. Iron deficiency and angiogenesis
title_full_unstemmed Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis. Iron deficiency and angiogenesis
title_short Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis. Iron deficiency and angiogenesis
title_sort effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis. iron deficiency and angiogenesis
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936284/
https://www.ncbi.nlm.nih.gov/pubmed/20723262
http://dx.doi.org/10.1186/1475-2867-10-28
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