Mg-based materials diminish tumor spreading and cancer metastases

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.

Slow degrading Mg-based materials induce tumor cell dormancy on an osteosarcoma-fibroblast coculture model

Osteosarcoma is one of the most common cancers in young adults and is commonly treated using surgery and chemotherapy.During the past years,these therapy approaches improved but failed to ameliorate the outcomes.Therefore,novel,targeted therapeutic approaches should be established to enhance treatment success while preserving patient’s quality of life.Recent studies suggest the application of degradable magnesium(Mg)alloys as orthopedic implants bearing a potential antitumor activity.Here,we examined the influence of Mg-based materials on an osteosarcoma-fibroblast coculture.Both,Mg and Mg-6Ag did not lead to tumor cell apoptosis at low degradation rates.Instead,the Mg-based materials induced cellular dormancy in the cancer cells indicated by a lower number of Ki-67 positive cancer cells and a higher p38 expression.This dormancy-like state could be reversed by reseeding on non-degrading glass slides but could not be provoked by inhibition of the protein kinase R-like endoplasmic reticulum kinase.By investigating the influence of the disjunct surface-near effects of the Mg degradation on cell proliferation,an increased pH was found to be a main initiator of Mg degradation-dependent tumor cell proliferation inhibition.