Reversing iron deficiency in liver tumor inhibited its progression
作者单位：second military medical university
会议名称：《中国营养学会第十五届全国营养科学大会》
会议日期：2022年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：iron metabolism hepatocarcinoma heme carrier protein 1 immune response metastasis
摘 要：Iron metabolism is dysregulated in hepatocellular carcinoma(HCC). Our previous study found that iron deficiency in HCC promoted its metastasis both through immunosuppressive and immune-indepentent manners. However the reason for iron deficiency in HCC and the potential effects of iron intervention on HCC progression were currently unkonwn. Methods Iron metabolic molecules were determined in clinical liver tumor samples and iron-deprived tumor cells to identify abnormally-expressed molecules. Then the functions of these molecules in regulating tumor iron content were verified and their expressions were observed in rats and mice with primary liver cancer. The iron intervention was conducted by targeting the key molecular and dietary iron supplement to reverse iron deficiency in liver tumor. The effects of iron intervention on tumor progression were determined and the role of immune responses were assessed by immune cells infiltration and immunodeficient mice. Results Firstly, we identified 3 iron transporters, STEAP3, DMT1, and HCP1, that altered free of iron status in liver tumor tissues. Among these, only silence or overexpression of HCP1 led to corresponding changes in intracellular iron content. Its expression was lost during the liver oncogenesis of rats and mice, along with the decrease of tumor iron content. Lentivirus-mediated regain of its expression increased iron content of liver cancer cells and restored the iron content of orthotopically implanted tumors. Functionally, the rebalance of iron metabolism, both by targeting HCP1 and dietary iron supplement, inhibited growth and metastasis of implanted tumors. The infiltrations of immune cells, mainly macrophages and natural killer cells, were increased by iron intervention. However, iron supplement accerlerated tumor progression in immunodeficient NCG mice, suggesting an essential role of immune responses. Conclusion In conclusion, these results showed that HCP1 downregulation led to iron deficiency in HCC, w