Tunneling nanotubes and cytonemes in cancer and development

Embryonic, adult, and cancer cells can exchange cytoplasmic proteins and even organelles using long, slender nanotubular interconnections. These cytoplasmic extensions, termed cytonemes, tunneling nanotubes, or tumor microtubes, span a spectrum of sizes. They have a structural core of F-actin filaments and can transport proteins and organelles ranging in size from small vesicles to mitochondria. These nanotubular interconnections can support embryonic development and tissue-tissue interactions as well as cancer cell defense against hypoxia, metabolic stressors, and chemotherapy. For example, tunneling nanotubes can transfer mitochondria to immune cells from non-malignant or tumor cells to promote or disable tumor cell killing. Numerous molecules initiate and maintain these nanotubular structures, suggesting cell type specificity. Many unanswered conceptual and mechanistic questions remain concerning the molecular and regulatory mechanisms driving their generation, structural and cell type-specific versus universal properties, and potential for novel therapeutic interventions-all providing exciting new opportunities in this rapidly expanding field of cell biology.