Study identifies DNA-carrying vesicles shed by migrating cancer cells

Researchers have described a population of large extracellular vesicles released as cancer cells migrate. The study, published in Nature Cell Biology on October 28, identifies structures termed motile vesicles, or MoVes, that contain DNA spanning the parent cell's genome as well as organelles and proteins. The work was led by Thupten Tsering and Julia Burnier and colleagues at McGill University and collaborating institutions. It asks how moving cancer cells release genetic material into their surroundings. It does not demonstrate a new treatment for cancer or establish that measuring these vesicles can diagnose a patient. Extracellular vesicles are membrane-bound structures that can carry material between cells. The researchers used live-cell imaging, electron microscopy, genomic and protein analyses to compare the newly observed structures with other vesicle populations. MoVes were approximately two to five micrometres across and formed around the trailing edge of migrating cells. Their production was associated with epithelial-to-mesenchymal transition, a process that can give cells greater mobility. Inducing that transition in non-tumourigenic cells increased MoVe production. This helps connect the observation to a biological process rather than simply to a static image of a cancer cell. The investigators also found mitochondrial cargo that could increase oxidative phosphorylation in recipient cells under experimental conditions. That is evidence of a functional effect in the systems tested. It does not, by itself, show that MoVes cause human metastasis or explain every way cancer spreads. The paper includes mouse biodistribution experiments as well as cell-based work. The authors report that injected vesicles accumulated in the liver and that higher doses could become trapped in the lungs, causing acute harm. Those experiments are not a proposed therapy, and their artificial delivery conditions should not be confused with the normal behaviour of vesicles in a patient. Several uncertainties remain. Isolating the structures involved procedures that could affect surrounding material and surface proteins. Different classes of large vesicles overlap in size and other features, making clean separation difficult. Some experimental inhibitors also affect broader cellular processes and cannot be assumed to act only on MoVes. Most importantly, the authors say the structures' functional roles in living organisms remain to be established. Whether they contribute to tumour progression, alter immune responses or offer useful biomarkers will require further study. The contribution of the report is a characterised mechanism of molecular release during cell movement, not a clinically proven discovery that can yet change an individual's care. Sources: www.nature.com · phys.org