TRIP Hemovigilance and Biovigilance Office, Leiden, The Netherlands; Erasmus University Medical Center Rotterdam, Department of Surgery, The Netherlands.
VU Medical Center Amsterdam, Department of Surgery, The Netherlands.
Med Hypotheses. 2018 Jan;110:110-113. doi: 10.1016/j.mehy.2017.12.011. Epub 2017 Dec 5.
In colorectal cancer patients, iron therapy, and especially intravenous iron therapy, is increasingly used to treat anemia and reduce the use of blood transfusions. However, iron has also been shown to be an essential nutrient for rapidly proliferating tissues and cells. In this respect, anemia of inflammation, characterized by limited duodenal iron uptake and sequestration of iron into the reticuloendothelial system, might be regarded as a potentially effective defense strategy of the human body against tumor growth. We therefore hypothesize that iron therapy, by supporting colorectal tumor growth and increasing the metastatic potential, may worsen tumor prognosis in colorectal cancer patients. This hypothesis is particularly supported for colorectal cancer by laboratory, epidemiological and animal studies, demonstrating the role of iron in all aspects of tumor development growth. Compared to non-malignant colon cells, tumor cells differ in the levels and activity of many iron import and export proteins, resulting in an increase in intracellular iron level and enhanced proliferation. In addition, it is demonstrated that iron is able to amplify Wnt signaling in tumors with Apc mutation, a critical mutation in the development of colorectal cancer. If our hypothesis is to be confirmed, current practice of iron administration, as treatment for anemia and as replacement of blood transfusions, can be hazardous and should be completely reconsidered.
在结直肠癌患者中，铁剂治疗，特别是静脉铁剂治疗，越来越多地被用于治疗贫血和减少输血。然而，铁也被证明是快速增殖组织和细胞的必需营养素。在这方面，炎症性贫血的特点是十二指肠铁摄取有限，铁被隔离到网状内皮系统，这可能被认为是人体对抗肿瘤生长的一种潜在有效防御策略。因此，我们假设铁剂治疗通过支持结直肠肿瘤生长和增加转移潜能，可能会使结直肠癌患者的肿瘤预后恶化。这一假设特别得到了实验室、流行病学和动物研究的支持，这些研究表明铁在肿瘤发展的各个方面都发挥了作用。与非恶性结肠细胞相比，肿瘤细胞在许多铁摄取和输出蛋白的水平和活性上存在差异，导致细胞内铁水平增加和增殖增强。此外，研究表明铁能够在 APC 突变的肿瘤中放大 Wnt 信号，APC 突变是结直肠癌发展的关键突变。如果我们的假设得到证实，目前用于治疗贫血和替代输血的铁剂治疗可能是危险的，应该彻底重新考虑。
