Tunneling nanotubes, TNT, communicate glioblastoma with surrounding non-tumor astrocytes to adapt them to hypoxic and metabolic tumor conditions
Silvana Valdebenito, Shaily Malik, Ross H. Luu, Olivier Loudig, Megan I. Mitchell, George Okafo, Krishna Bhat, Brendan Prideaux, Eliseo A. Eugenín
Abstract
Cell-to-cell communication is essential for the development and proper function of multicellular systems. We and others demonstrated that tunneling nanotubes (TNT) proliferate in several pathological conditions such as HIV, cancer, and neurodegenerative diseases. However, the nature, function, and contribution of TNT to cancer pathogenesis are poorly understood. Our analyses demonstrate that TNT structures are induced between glioblastoma (GBM) cells and surrounding non-tumor astrocytes to transfer tumor-derived mitochondria. The mitochondrial transfer mediated by TNT resulted in the adaptation of non-tumor astrocytes to tumor-like metabolism and hypoxia conditions. In conclusion, TNT are an efficient cell-to-cell communication system used by cancer cells to adapt the microenvironment to the invasive nature of the tumor.