Integrin α10-Antibodies Reduce Glioblastoma Tumor Growth and Cell Migration

SIMPLE SUMMARY: Glioblastoma (GB) is the most common and most deadly form of brain tumor in adults which currently lacks effective treatments. Thus, there is a high need to identify new and effective ways to target the aggressive GB cells and treat the GB patients. In this study, we investigated the treatment effect of two antibodies that have been developed to target the protein integrin α10β1, which is present on the surface of GB cells. Our results show that the growth of GB tumor cells is reduced in the presence of the α10β1 antibodies. The treatment effect is demonstrated both in cell experiments and in an animal model. In addition, we found that the antibodies reduce the migration of the GB cells. We suggest that function-blocking antibodies targeting the integrin α10β1 is a promising new approach to treat glioblastoma patients. ABSTRACT: Glioblastoma (GB) is the most common and the most aggressive form of brain tumor in adults, which currently lacks efficient treatment strategies. In this study, we investigated the therapeutic effect of function-blocking antibodies targeting integrin α10β1 on patient-derived-GB cell lines in vitro and in vivo. The in vitro studies demonstrated significant inhibiting effects of the integrin α10 antibodies on the adhesion, migration, proliferation, and sphere formation of GB cells. In a xenograft mouse model, the effect of the antibodies on tumor growth was investigated in luciferase-labeled and subcutaneously implanted GB cells. As demonstrated by in vivo imaging analysis and caliper measurements, the integrin α10-antibodies significantly suppressed GB tumor growth compared to control antibodies. Immunohistochemical analysis of the GB tumors showed lower expression of the proliferation marker Ki67 and an increased expression of cleaved caspase-3 after treatment with integrin α10 antibodies, further supporting a therapeutic effect. Our results suggest that function-blocking antibody targeting integrin α10β1 is a promising therapeutic strategy for the treatment of glioblastoma.