Previously unappreciated form of cell-to-cell communication might be related to prions and may participate in cancer metastasis and infections

Scientists know that some cells build wire-like extensions as a kind of temporary foothold to move themselves from place to place. But these “extensions” might in fact be involved in something far more complex [see attached article]. In 1999, cell biologist Thomas Kornberg (Uni­v California, San Francisco) was studying how fly larvae develop wings, and he noticed a sea of filaments –– projecting from the wing buds toward the signaling center that is essential for their growth. He coined the term cyto­neme — or cell thread — to describe these fila­ments. In 2004, two research groups independently pub­lished observations of “nanotubes in mammalian cells” that seemed to move cargo (i.e. organelles and vesicles) back and forth. These accidental sightings grew into a Science paper that described the structures as “nano­tubular highways”. These researchers proceeded to describe different sorts of nanotubes –– some holding subcellular vesicles and mitochondria inside, and others holding bacteria.

Meanwhile, other labs have reported cell-connecting tubes in neurons, epithelial cells, mesenchymal stem cells, several types of immune cells, and multiple cancers. Some tubes end in gap junctions: gateways that bestow the neuron-like ability to send electrical signals, which can also pass along peptides and RNA molecules. There is speculation that such connections may be more than conceptually related to neuronal synapses. The strongest evidence for a role in disease came in 2015, when a team of researchers was watching human gliomas grow in culture. Cells derived from the tumors were injected into the brains of mice that had glass windows in their skulls — through which they could watch the cells. As tumor cells invaded, they sent tubular protrusions ahead of them; they saw many tubes connecting cells through gap junctions. Interconnected cells managed to survive doses of radiation that had killed isolated cells, apparently because the gap junctions helped to spread the load of toxic ions to neighbors.

When radiation did kill linked tumor cells, nuclei from those cells sometimes traveled down a nanotube, to form a vigorous new cancer cell. These ‘tumor micro­tubes’ were also found in biopsies from patients; denser longer tubes correlated with more resistant forms of cancer and a poorer progno­sis for the patient. It has been speculated that cancer drugs such as paclitaxel –– that appear to work by disrupting tumor microtubules –– might be keeping these tubes from sprouting or extending, leading to effective treatment against certain types of cancer. The entire field remains controversial at this moment, with some suggesting these nanotubes are artifacts seen only in cell culture, while others disagree with these suggestions. Stay tuned..!

Nature 21 Sept 2o17; 549: 322–324

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