Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis. Iron deficiency and angiogenesis.
Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis. Iron deficiency and angiogenesis.
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DOI：
10.1186/1475-2867-10-28
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发表时间：
2010-08-19
影响因子：
5.8
通讯作者：
Huang X
中科院分区：
文献类型：
--
作者：
Eckard J;Dai J;Wu J;Jian J;Yang Q;Chen H;Costa M;Frenkel K;Huang X
众所周知，被诊断患有乳腺癌的年轻女性的死亡率高于老年患者。导致这种较差结果的具体风险因素尚未确定。在本研究中，我们假设缺铁是年轻女性的一种常见疾病，它通过促进缺氧诱导因子 1α（HIF-1α 和血管内皮生长因子（VEGF））的形成而导致不良预后。这一假设在体外细胞培养模型系统中进行了测试。用转铁蛋白受体 1（TfR1）shRNA 转染人乳腺癌 MDA-MB-231 细胞， 本质上损害铁的吸收。细胞铁状态由一组铁蛋白确定，血管生成由细胞中 VEGF 水平以及小鼠异种移植模型评估。与亲代细胞相比，在 TfR1 敲低的 MDA-MB-231 细胞中观察到铁蛋白显着降低，同时 VEGF 增加。 TfR1 shRNA 转染子也引起了更强的 将细胞皮下注射到裸鼠体内后的血管生成反应。分子机制似乎是细胞缺铁通过稳定 HIF-1α 来促进 VEGF 形成。这种机制在人类乳腺癌MCF-7和肝癌HepG2细胞中也成立。细胞缺铁会增加 HIF-1α、VEGF 和血管生成，表明全身缺铁可能在肿瘤血管生成中发挥重要作用 以及这一年轻乳腺癌患者群体的复发情况。
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. 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. 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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影响因子：
4
作者：
Chen, Chien-Lin;Hsieh, Yeun-Ting;Chen, Hong-Chen
通讯作者：
Chen, Hong-Chen
影响因子：
8.8
作者：
Hardman, WE;Barnes, CJ;Cameron, IL
通讯作者：
Cameron, IL
影响因子：
48
作者：
Lee, Genee Y.;Kenny, Paraic A.;Bissell, Mina J.
通讯作者：
Bissell, Mina J.
影响因子：
3.8
作者：
Han W;Kim SW;Park IA;Kang D;Kim SW;Youn YK;Oh SK;Choe KJ;Noh DY
通讯作者：
Noh DY
影响因子：
6
作者：
Dongiovanni, Paola;Valenti, Luca;Fargion, Silvia
通讯作者：
Fargion, Silvia