[HTML][HTML] Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis.

J Eckard, J Dai, J Wu, J Jian, Q Yang, H Chen… - Cancer cell …, 2010 - Springer
J Eckard, J Dai, J Wu, J Jian, Q Yang, H Chen, M Costa, K Frenkel, X Huang
Cancer cell international, 2010Springer
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 …
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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