Globig Philipp, Madurawala Roshani, Willumeit-Römer Regine, Martini Fernanda, Mazzoni Elisa, Luthringer-Feyerabend Bérengère J C
Institute of Metallic Biomaterials, Helmholtz-Zentrum Hereon GmbH, 21502, Geesthacht, Germany.
Department of Medical Sciences, University of Ferrara, 44121, Ferrara, Italy.
Bioact Mater. 2022 May 10;19:594-610. doi: 10.1016/j.bioactmat.2022.05.002. eCollection 2023 Jan.
Cancer metastases are the most common causes of cancer-related deaths. The formation of secondary tumors at different sites in the human body can impair multiple organ function and dramatically decrease the survival of the patients. In this stage, it is difficulty to treat tumor growth and spreading due to arising therapy resistances. Therefore, it is important to prevent cancer metastases and to increase subsequent cancer therapy success. Cancer metastases are conventionally treated with radiation or chemotherapy. However, these treatments elicit lots of side effects, wherefore novel local treatment approaches are currently discussed. Recent studies already showed anticancer activity of specially designed degradable magnesium (Mg) alloys by reducing the cancer cell proliferation. In this work, we investigated the impact of these Mg-based materials on different steps of the metastatic cascade including cancer cell migration, invasion, and cancer-induced angiogenesis. Both, Mg and Mg-6Ag reduced cell migration and invasion of osteosarcoma cells in coculture with fibroblasts. Furthermore, the Mg-based materials used in this study diminished the cancer-induced angiogenesis. Endothelial cells incubated with conditioned media obtained from these Mg and Mg-6Ag showed a reduced cell layer permeability, a reduced proliferation and inhibited cell migration. The tube formation as a last step of angiogenesis was stimulated with the presence of Mg under normoxia and diminished under hypoxia.
癌症转移是癌症相关死亡的最常见原因。人体不同部位继发性肿瘤的形成会损害多个器官的功能，并显著降低患者的生存率。在这个阶段，由于出现治疗抗性，治疗肿瘤生长和扩散很困难。因此，预防癌症转移并提高后续癌症治疗的成功率很重要。传统上，癌症转移采用放疗或化疗进行治疗。然而，这些治疗会引发许多副作用，因此目前正在讨论新的局部治疗方法。最近的研究已经表明，通过减少癌细胞增殖，特殊设计的可降解镁（Mg）合金具有抗癌活性。在这项工作中，我们研究了这些镁基材料对转移级联反应不同步骤的影响，包括癌细胞迁移、侵袭和癌症诱导的血管生成。镁和镁-6银都减少了与成纤维细胞共培养时骨肉瘤细胞的迁移和侵袭。此外，本研究中使用的镁基材料减少了癌症诱导的血管生成。用从这些镁和镁-6银获得的条件培养基培养的内皮细胞显示细胞层通透性降低、增殖减少和细胞迁移受到抑制。作为血管生成最后一步的管形成在常氧条件下受到镁的刺激，而在缺氧条件下则减少。
