Duan Xiaoyue, He Kun, Li Jing, Cheng Man, Song Hongjiao, Liu Jinqiu, Liu Ping
School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University Shanghai, People's Republic of China.
Int J Physiol Pathophysiol Pharmacol. 2018 Apr 20;10(2):105-114. eCollection 2018.
Cancer cells exhibit an increasing iron demand associated with the tumor progression. But the mechanism of iron accumulation in the tumor microenvironment is still unclear. Tumor associated macrophages (TAMs) in the tumor microenvironment may act as extra iron source. However, evidence is still lacking in TAMs as iron donors. In the present study, we found that iron concentration was significantly increased at tumor metastatic stage, which could be attributed to up-regulated expression of lipocalin2 (Lcn2). TAMs in the microenvironment secreted Lcn2. Moreover, TAMs increased intracellular iron concentration in tumor cells via Lcn2 as transporter, which could be restored by Lcn2 antibody neutralization. In conclusion, TAMs increased intracellular iron concentration of the tumor cells via Lcn2 which acted as an iron transporter. Targeting Lcn2 secretion in TAMs to "starve cancer cells" could act as alternative option for tumor therapy.
癌细胞表现出与肿瘤进展相关的铁需求增加。但肿瘤微环境中铁积累的机制仍不清楚。肿瘤微环境中的肿瘤相关巨噬细胞（TAM）可能作为额外的铁源。然而，关于TAM作为铁供体的证据仍然不足。在本研究中，我们发现肿瘤转移阶段铁浓度显著增加，这可能归因于脂质运载蛋白2（Lcn2）表达上调。微环境中的TAM分泌Lcn2。此外，TAM通过Lcn2作为转运体增加肿瘤细胞内铁浓度，Lcn2抗体中和可使其恢复。总之，TAM通过作为铁转运体的Lcn2增加肿瘤细胞内铁浓度。靶向TAM中Lcn2的分泌以“饿死癌细胞”可能成为肿瘤治疗的替代选择。
