（生物谷Bioon.com）—一項(xiàng)新的研究發(fā)表于Science Translational Medicine,該研究提示對(duì)鐵調(diào)控的改變可能是乳腺癌生長(zhǎng)和擴(kuò)散的一個(gè)重要的驅(qū)動(dòng)因素，它可能被用來(lái)預(yù)測(cè)罹患乳腺癌婦女的存活情況,。
盡管幾乎所有的細(xì)胞的生長(zhǎng)都需要鐵,，這種強(qiáng)力的金屬如果在細(xì)胞中沒(méi)有受到嚴(yán)密調(diào)控的話(huà)，它可帶來(lái)災(zāi)難,。 如今,，F(xiàn)rank Torti及其同事顯示，鐵轉(zhuǎn)運(yùn)蛋白（這是一種將鐵從細(xì)胞中轉(zhuǎn)運(yùn)出來(lái)的蛋白）濃度與癌癥擴(kuò)散到身體其它部位的可能性有關(guān)聯(lián),，并可能成為預(yù)測(cè)病人治療效果的一個(gè)指示性的信號(hào),。 應(yīng)用鐵轉(zhuǎn)運(yùn)蛋白作為鐵調(diào)控的一個(gè)標(biāo)記因此可成為預(yù)測(cè)乳腺癌治療效果的一個(gè)有用的工具,，且甚至可能幫助指導(dǎo)治療。 在將來(lái),，操縱鐵轉(zhuǎn)運(yùn)蛋白的濃度或可影響鐵轉(zhuǎn)運(yùn)蛋白濃度的蛋白也可能被證明是一種有效治療乳腺癌的方法,。
在本研究中，研究人員發(fā)現(xiàn),，在乳腺腫瘤中的鐵轉(zhuǎn)運(yùn)蛋白水平比正常組織中的鐵轉(zhuǎn)運(yùn)蛋白水平明顯要低,。 在沒(méi)有足夠的鐵轉(zhuǎn)運(yùn)蛋白將鐵從細(xì)胞中轉(zhuǎn)運(yùn)出來(lái)的時(shí)候，一種“游離”鐵的有害的積聚便發(fā)生了,。 然而,，Torti及其同事發(fā)現(xiàn)，這一過(guò)程是可改變的,；在小鼠體內(nèi)生長(zhǎng)的人類(lèi)乳腺腫瘤,，在其鐵轉(zhuǎn)運(yùn)蛋白水平恢復(fù)正常之后，其腫瘤生長(zhǎng)的速度要比那些體內(nèi)鐵轉(zhuǎn)運(yùn)蛋白水平低下的腫瘤慢,。 接下來(lái)，該研究團(tuán)隊(duì)觀察了超過(guò)800名的罹患乳腺癌的婦女的基因表達(dá)譜,。 通過(guò)確定鐵轉(zhuǎn)運(yùn)蛋白及另外一種與鐵有關(guān)的蛋白（被稱(chēng)作肝抗菌肽,，hepcidin）的水平，研究人員可根據(jù)病患癌癥擴(kuò)散的可能性將這些婦女進(jìn)行分組,。 從這些數(shù)據(jù)中,，研究人員發(fā)現(xiàn)，鐵轉(zhuǎn)運(yùn)蛋白水平低下是罹患乳腺癌婦女的一個(gè)很強(qiáng)的預(yù)測(cè)病人治療效果不良的預(yù)測(cè)因子,。 一個(gè)正面的情況是,，他們也發(fā)現(xiàn)，鐵轉(zhuǎn)運(yùn)蛋白水平高對(duì)乳腺癌患者是一個(gè)良好的征兆,，它可預(yù)測(cè)90%的10年存活率,。
究竟為什么細(xì)胞中游離鐵含量高會(huì)促使癌癥變得更具侵略性依然不清楚，但這些結(jié)果顯示,，在乳腺癌中對(duì)鐵處置的變化可強(qiáng)有力地促進(jìn)癌癥的生長(zhǎng),。
凝聚社會(huì)力量 共抗癌癥--生物谷專(zhuān)訪(fǎng)中山大學(xué)腫瘤防治中心錢(qián)朝南研究員
關(guān)于乳腺癌的最新研究進(jìn)展
FASEB：橄欖油有助預(yù)防乳腺癌
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Nature Cell Biology ：miR-9可控制乳腺癌擴(kuò)散
生物谷推薦原文出處：
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.
