McGill researchers discover new DNA-carrying vesicles from migrating cancer cells

Researchers at the McGill University Health Centre have discovered a new type of extracellular vesicle that migrating cancer cells use to shed their DNA. The finding, published in Nature Cell Biology, reveals a previously unknown biological process that could provide insights into how cancer spreads. The team named the structures motile vesicles, or MoVes. They found MoVes carry the entire genome of the parent cell, including cancer-associated mutations.

"Extracellular vesicles, or EVs, have been studied for decades, yet we are still discovering entirely new ways in which cells produce and release them," said Prof. Julia Burnier, the study's senior author and a scientist at the MUHC Research Institute. "Studying this new type of vesicle, which we’ve named MoVes, could uncover new mechanisms involved in cancer progression and ultimately reveal new therapeutic targets." The discovery was unexpected, said first author and PhD student Thupten Tsering. "We were trying to understand how cancer cells release DNA and unexpectedly uncovered a biological process through which migrating cancer cells release genetic material and communicate with their surroundings," Tsering said.

Extracellular vesicles are tiny, bubble-like structures released by cells that travel through body fluids like blood. They carry molecular cargo, including DNA, and can influence other cells. In cancer, some vesicles are thought to help prepare distant organs for metastasis or make cells resistant to treatment. The research team used genomic analyses and advanced imaging to study cancerous and non-cancerous cell lines. They collaborated with Dr. David Lyden at Weill Cornell Medical College to develop methods to isolate MoVes from other vesicles.

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The researchers found MoVes are distinct from other extracellular vesicles. "Unlike previously described EVs, MoVes are specifically formed at the trailing edge of migrating cells through a distinct biological process," said Tsering. "They are relatively large (2–5 µm), carry the entire parental cell genome as well as functional organelles." Production of MoVes was strongly linked to a cellular process called epithelial-to-mesenchymal transition, or EMT. This process allows cells to become mobile and invasive, which is associated with cancer progression.

"The breakthrough came when we induced EMT in non-cancerous cells, making them more mobile," explained Burnier, who is also an associate professor at McGill University. "We saw a dramatic increase in MoVes production, establishing a direct link between EMT and cell migration and the formation of these vesicles." The team also observed that aggressive triple-negative breast cancer cells produced far more MoVes than non-cancerous breast cells. Burnier's team is now working to understand how MoVes are formed and what effects their molecular cargo has on receiving cells. This could help determine if they play a direct role in cancer progression and identify ways to block that process. The researchers also hope to confirm whether MoVes can be detected in animal models and in patients. If so, they could be investigated as potential biomarkers to help detect cancer or monitor its response to treatment. The study was supported by the Canadian Institutes of Health Research. Burnier was supported by the Fonds de recherche du Québec, and Tsering received funding from multiple sources including the FRQ and the McGill University Health Centre Foundation. Key research support was provided by the Centre for Applied Nanomedicine and proteomics platform at the MUHC Research Institute, as well as McGill University’s Facility for Electron Microscopy Research and McGill Genome Centre.

With files from McGill University