Tunneling Nanotubes: The Fuel of Tumor Progression?

Tunneling nanotubes (TNTs) are thin membrane tubes connecting remote cells and allowing the transfer of cellular content. TNTs have been reported in several cancer in vitro, ex vivo, and in vivo models. Cancer cells exploit TNT-like connections to exchange material between themselves or with the tumoral microenvironment. Cells acquire new abilities (e.g., enhanced metabolic plasticity, migratory phenotypes, angiogenic ability, and therapy resistance) via these exchanges, contributing to cancer aggressiveness. Here, we review the morphological and functional features of TNT-like structures and their impact on cancer progression and resistance to therapies. Finally, we discuss the case of glioblastoma (GBM), in which a functional and resistant network between cancer cells in an in vivo model has been described for the first time.