Freitas Isabel, Boncompagni Eleonora, Vaccarone Rita, Fenoglio Carla, Barni Sergio, Baronzio Gian Franco
Department of Animal Biology and CNR-IGM, University of Pavia, 27100 Pavia, Italy.
Anticancer Res. 2007 Sep-Oct;27(5A):3059-65.
Iron is indispensable for the metabolism and proliferation of both normal and malignant cells. Recycling from senescent erythrocytes in the liver and spleen is critical for iron supply to all tissues. In the liver and spleen from MMTV-neu (erbB-2) mice bearing a mammary carcinoma, we noticed the scarcity of hemosiderin pigment and its abundance in the stroma of the tumor. Thus iron (III) was investigated with the Perls' reaction in tissues from normal and MMTV-neu mice. With respect to normal animals, in MMTV-neu mice, staining for iron was almost absent in the liver and scarce in the red pulp of the spleen. By contrast, iron was abundant in stromal and tumor cells in the invasion, angiogenic, necrotic and hemorrhagic regions and also in the interstitial fluid. These observations suggest that the tumor subverts iron recycling to its own advantage, by directly utilizing iron released from erythrocytes and dead tumor cells. Our findings are in keeping with the development of iron chelating drugs as chemotherapic agents.
铁对于正常细胞和恶性细胞的代谢及增殖均不可或缺。肝脏和脾脏中衰老红细胞的铁循环对于向所有组织供应铁至关重要。在患有乳腺癌的MMTV-neu(erbB-2)小鼠的肝脏和脾脏中,我们注意到含铁血黄素色素稀少,而在肿瘤基质中却大量存在。因此,我们用Perls反应对正常小鼠和MMTV-neu小鼠的组织中的铁(III)进行了研究。与正常动物相比,在MMTV-neu小鼠中,肝脏几乎没有铁染色,脾脏红髓中铁染色稀少。相比之下,在侵袭、血管生成、坏死和出血区域的基质和肿瘤细胞以及间质液中,铁含量丰富。这些观察结果表明,肿瘤通过直接利用从红细胞和死亡肿瘤细胞释放的铁,将铁循环转变为自身优势。我们的发现与铁螯合药物作为化疗药物的发展相一致。