Tunneling nanotubes: The intercellular conduits contributing to cancer pathogenesis and its therapy

Abstract

Tunneling nanotubes (TNTs) are intercellular conduits which meet the communication needs of non-adjacent cells situated in the same tissue but at distances up to a few hundred microns. TNTs are unique type of membrane protrusion which contain F-actin and freely hover over substratum in the extracellular space to connect the distant cells. TNTs, known to form through actin remodeling mechanisms, are intercellular bridges that connect cytoplasm of two cells, and facilitate the transfer of organelles, molecules, and pathogens among the cells. In tumor microenvironment, TNTs act as communication channel among cancer, normal, and immune cells to facilitate the transfer of calcium waves, mitochondria, lysosomes, and proteins, which in turn contribute to the survival, metastasis, and chemo-resistance in cancer cells. Recently, TNTs were shown to mediate the transfer of nanoparticles, drugs, and viruses between cells, suggesting that TNTs could be exploited as a potential route for delivery of anti-cancer agents and oncolytic viruses to the target cells. The present review discusses the emerging concepts and role of TNTs in the context of chemo- and radio-resistance with implications in the cancer therapy.

Keywords: Bystander effect; Cancer therapy; Intercellular conduits; Tumor microenvironment; Tunneling nanotubes.