Lost in translation: applying 2D intercellular communication via tunneling nanotubes in cell culture to physiologically relevant 3D microenvironments

Tunneling nanotubes (TNTs) are membranous conduits for direct cell-to-cell communication. Until the past decade, little had been known about their composite structure, function, and mechanisms of action in both normal physiologic conditions as well as in disease states. Now TNTs are attracting increasing interest for their key role(s) in the pathogenesis of disease, including neurodegenerative disorders, inflammatory and infectious diseases, and cancer. The field of TNT biology is still in its infancy, but inroads have been made in determining potential mechanisms and function of these remarkable structures. For example, TNTs function as critical conduits for cellular exchange of information; thus, in cancer, they may play an important role in critical pathophysiologic features of the disease, including cellular invasion, metastasis, and emergence of chemotherapy drug resistance. Although the TNT field is still in a nascent stage, we propose that TNTs can be investigated as novel targets for drug-based treatment of cancer and other diseases.