Cancer cells are known to hijack energy-generating components from neurons, facilitating their spread to remote locations. This groundbreaking discovery may enhance treatments for the most aggressive tumors.

“This marks the first instance of mitochondrial transfer from nerves to cancer cells,” states Elizabeth Lepasky, who is not directly linked to the study conducted at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. “This signifies a pivotal advancement in cancer neuroscience, a rapidly evolving field.”

Prior knowledge indicated that both intratumor and adjacent tumors produce proteins and electrical impulses that promote cancer growth and dissemination. “A higher density of nerves within tumors correlates with a poorer prognosis,” says Simone Grelet from the University of Southern Alabama.

Earlier investigations have demonstrated that brain tumor cells can absorb mitochondria (the energy-producing organelles) from non-neuronal brain cells. However, the potential for tumor cells to extract mitochondria from neurons remained unclear, according to Grelet.

To explore this, Grelet and his team genetically modified breast cancer cells derived from mice to contain red fluorescent molecules and combined them with mouse neurons that had mitochondria labeled with green pigments in laboratory conditions. Imaging revealed that cancer cells can seize mitochondria from neurons within a matter of hours.

“Cancer cells extend their membranes to absorb mitochondria from neurons,” explains Grelet. “It’s akin to a lineup of mitochondria filtering through a narrow passage, entering the cancer cells sequentially.”

To assess whether this phenomenon occurs in vivo, the researchers injected red breast cancer cells into the mammary glands of female mice to induce tumor growth. They also genetically engineered the surrounding nerves to carry green mitochondria. Approximately one month later, 2% of the cancer cells in these tumors had taken up mitochondria from neurons.

Conversely, 14% of tumor cells that metastasized to the brain exhibited neuronal-derived mitochondria. This suggests that cancer cells acquiring mitochondria from nerves have a significant advantage over other cancer types. Further tests indicate that these mitochondria contribute to greater resilience against the physical and chemical challenges encountered in the bloodstream.

“Cancer cells face numerous hurdles in their migration,” remarks Repasky. “They must escape the primary tumor, navigate barriers to blood vessels, exit the bloodstream, and secure sufficient oxygen and nutrients at secondary sites. By appropriating mitochondria, it appears cancer cells can endure this tumultuous journey,” she adds.

To determine if this process also occurs in humans, researchers examined tumor samples from eight women with metastatic breast cancer. They discovered that tumor cells from distant sites contained, on average, 17% more mitochondria compared to those from breast tumors, suggesting that similar mechanisms are at play in patients, according to Grelet.

Moreover, the team analyzed human prostate tumor samples and observed that cancer cells near nerves contained significantly more mitochondria than those situated further away. “I believe this represents a common mechanism utilized by various tumor types,” asserts team member Gustavo Ayala from the University of Texas Health Science Center in Houston.

The findings indicate that inhibiting mitochondrial transfer could potentially curtail the spread of the deadliest tumors. “We are optimistic that this is achievable, at least for certain tumor types,” Repasky suggests. Ayala mentions that they are working towards developing a drug to facilitate this approach.