（生物谷Bioon.com）—一项新的研究发表于Science Translational Medicine,该研究提示对铁调控的改变可能是乳腺癌生长和扩散的一个重要的驱动因素，它可能被用来预测罹患乳腺癌妇女的存活情况。
尽管几乎所有的细胞的生长都需要铁，这种强力的金属如果在细胞中没有受到严密调控的话，它可带来灾难。 如今，Frank Torti及其同事显示，铁转运蛋白（这是一种将铁从细胞中转运出来的蛋白）浓度与癌症扩散到身体其它部位的可能性有关联，并可能成为预测病人治疗效果的一个指示性的信号。 应用铁转运蛋白作为铁调控的一个标记因此可成为预测乳腺癌治疗效果的一个有用的工具，且甚至可能帮助指导治疗。 在将来，操纵铁转运蛋白的浓度或可影响铁转运蛋白浓度的蛋白也可能被证明是一种有效治疗乳腺癌的方法。
在本研究中，研究人员发现，在乳腺肿瘤中的铁转运蛋白水平比正常组织中的铁转运蛋白水平明显要低。 在没有足够的铁转运蛋白将铁从细胞中转运出来的时候，一种“游离”铁的有害的积聚便发生了。 然而，Torti及其同事发现，这一过程是可改变的；在小鼠体内生长的人类乳腺肿瘤，在其铁转运蛋白水平恢复正常之后，其肿瘤生长的速度要比那些体内铁转运蛋白水平低下的肿瘤慢。 接下来，该研究团队观察了超过800名的罹患乳腺癌的妇女的基因表达谱。 通过确定铁转运蛋白及另外一种与铁有关的蛋白（被称作肝抗菌肽，hepcidin）的水平，研究人员可根据病患癌症扩散的可能性将这些妇女进行分组。 从这些数据中，研究人员发现，铁转运蛋白水平低下是罹患乳腺癌妇女的一个很强的预测病人治疗效果不良的预测因子。 一个正面的情况是，他们也发现，铁转运蛋白水平高对乳腺癌患者是一个良好的征兆，它可预测90%的10年存活率。
究竟为什么细胞中游离铁含量高会促使癌症变得更具侵略性依然不清楚，但这些结果显示，在乳腺癌中对铁处置的变化可强有力地促进癌症的生长。
凝聚社会力量 共抗癌症--生物谷专访中山大学肿瘤防治中心钱朝南研究员
关于乳腺癌的最新研究进展
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生物谷推荐原文出处：
Sci Transl Med DOI: 10.1126/scisignal.3001127
Ferroportin and Iron Regulation in Breast Cancer Progression and Prognosis
Zandra K. Pinnix1, Lance D. Miller2,3, Wei Wang2, Ralph D’Agostino Jr.3,4, Tim Kute5, Mark C. Willingham3,5, Heather Hatcher2, Lia Tesfay2, Guangchao Sui2, Xiumin Di2, Suzy V. Torti1,3 and Frank M. Torti2,3,*
Ferroportin and hepcidin are critical proteins for the regulation of systemic iron homeostasis. Ferroportin is the only known mechanism for export of intracellular non–heme-associated iron; its stability is regulated by the hormone hepcidin. Although ferroportin profoundly affects concentrations of intracellular iron in tissues important for systemic iron absorption and trafficking, ferroportin concentrations in breast cancer and their influence on growth and prognosis have not been examined. We demonstrate here that both ferroportin and hepcidin are expressed in cultured human breast epithelial cells and that hepcidin regulates ferroportin in these cells. Further, ferroportin protein is substantially reduced in breast cancer cells compared to nonmalignant breast epithelial cells; ferroportin protein abundance correlates with metabolically available iron. Ferroportin protein is also present in normal human mammary tissue and markedly decreased in breast cancer tissue, with the highest degree of anaplasia associated with lowest ferroportin expression. Transfection of breast cancer cells with ferroportin significantly reduces their growth after orthotopic implantation in the mouse mammary fat pad. Gene expression profiles in breast cancers from >800 women reveal that decreased ferroportin gene expression is associated with a significant reduction in metastasis-free and disease-specific survival that is independent of other breast cancer risk factors. High ferroportin and low hepcidin gene expression identifies an extremely favorable cohort of breast cancer patients who have a 10-year survival of >90%. Ferroportin is a pivotal protein in breast biology and a strong and independent predictor of prognosis in breast cancer.
1Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
2Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
3Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
4Department of Biostatistics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
5Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
