Abstract
Intercellular communication in the tumor microenvironment has a major impact on therapeutic outcomes. In particular, highly aggressive cancers such as glioblastoma benefit from efficient cellular communication by developing resistance to therapy or by infiltrating surrounding tissue to escape radiotherapy. Tiny membrane tunnels, such as tunneling nanotubes (TNTs), can serve as an effective communication tool for tumor cells. With these structures, the cells can build a large network that allows them to react and adapt to their environment as quickly as possible, thereby combating the therapy. In this study, we investigated the effects of chemotherapeutic agents on TNT networks in U87 MG cells to determine if they affect the number of TNTs and, consequently, possible therapeutic outcomes. The effect of drugs on TNT stability may be related to their effects on actin and tubulin, which are known stabilizers of membrane structures. Therefore, we also analyzed the cytoskeletal content of TNTs in U87 MG cells and examined the effect of the actin polymerization inhibitor cytochalasin B (CytoB) on TNT formation and networks. CytoB reduced the number of TNTs in this study, suggesting that actin, as a cytoskeletal component, is required for developing TNT networks. In contrast, the chemotherapeutic agents temozolomide (TMZ) and cytarabine (AraC) do not affect TNTs and actin content. As TNT networks are closely linked to increased therapy resistance of certain tumors, we believe that the lack of suppression of TNTs is a major problem in current glioblastoma therapy and should be a target for further research in the future.