Department of Health Sciences and Technology, Institute for Translational Medicine, ETH Zurich, CH-8092 Zurich, Switzerland.
Int J Mol Sci. 2021 Jan 6;22(2):498. doi: 10.3390/ijms22020498.
Interest has grown in harnessing biological agents for cancer treatment as dynamic vectors with enhanced tumor targeting. While bacterial traits such as proliferation in tumors, modulation of an immune response, and local secretion of toxins have been well studied, less is known about bacteria as competitors for nutrients. Here, we investigated the use of a bacterial strain as a living iron chelator, competing for this nutrient vital to tumor growth and progression. We established an in vitro co-culture system consisting of the magnetotactic strain AMB-1 incubated under hypoxic conditions with human melanoma cells. Siderophore production by 10 AMB-1/mL in human transferrin (Tf)-supplemented media was quantified and found to be equivalent to a concentration of 3.78 µM ± 0.117 µM deferoxamine (DFO), a potent drug used in iron chelation therapy. Our experiments revealed an increased expression of transferrin receptor 1 (TfR1) and a significant decrease of cancer cell viability, indicating the bacteria's ability to alter iron homeostasis in human melanoma cells. Our results show the potential of a bacterial strain acting as a self-replicating iron-chelating agent, which could serve as an additional mechanism reinforcing current bacterial cancer therapies.
人们对利用生物制剂作为具有增强肿瘤靶向性的动态载体来治疗癌症产生了浓厚的兴趣。虽然细菌的一些特性，如在肿瘤中增殖、调节免疫反应和局部分泌毒素等已经得到了充分的研究，但关于细菌作为营养物质竞争者的了解较少。在这里，我们研究了利用一种细菌菌株作为一种活的铁螯合剂，与肿瘤生长和进展所必需的这种营养物质竞争。我们建立了一个体外共培养系统，由在缺氧条件下孵育的磁细菌菌株 AMB-1 和人黑色素瘤细胞组成。在含有人转铁蛋白（Tf）的培养基中，10 AMB-1/mL 细菌产生的铁载体被定量，并发现其相当于 3.78 µM ± 0.117 µM 去铁胺（DFO）的浓度，DFO 是一种用于铁螯合治疗的有效药物。我们的实验揭示了转铁蛋白受体 1（TfR1）的表达增加和癌细胞活力的显著下降，表明细菌有能力改变人黑色素瘤细胞中的铁平衡。我们的结果表明，一种细菌菌株作为一种自我复制的铁螯合剂具有潜力，它可以作为一种额外的机制来加强当前的细菌癌症治疗。
