After a stroke, the brain gets to work repairing damaged tissue. But new research suggests some of the same biological processes that aid recovery may also help tumor cells grow and spread.
In a study published in Nature Cancer , researchers found that ischemic stroke — caused by blocked blood flow to the brain — altered the environment surrounding gliomas, a form of brain cancer, in ways that accelerated tumor progression.
“What we found is that glioma cells can take advantage of the same processes the brain uses to repair itself after an injury to help the tumor progress,” said Qi Ye, assistant professor at the Fralin Biomedical Research Institute Cancer Research Center in Washington, D.C., and co-first author of the study. “They integrate into the brain and use every chance to progress. We need to understand how they do that and then find ways to stop it.”
The findings do not mean that having a stroke causes brain cancer, Ye said. The causes of most gliomas remain unknown, and the clinical association between a prior history of brain injury and later brain tumors does not prove that one causes the other.
Instead, this study asked whether a prior history of stroke can change the brain environment in ways that promote glioma progression. The researchers found that stroke can reshape the tumor environment and accelerate glioma growth and spread.
Previous population studies had reported an association between brain injury, including stroke, and brain tumors. But scientists did not understand the biological mechanisms that might connect the two.
Using multiple experimental models, including models incorporating glioma cells derived from patients, the researchers consistently found that stroke accelerated glioma growth and increased the spread of tumor cells into areas of the brain affected by stroke.
Ye began the research while a postdoctoral associate at Baylor, where most of the experimental work was conducted before she came to Virginia Tech.
Christine Madamba of Baylor College of Medicine and the Duncan Neurological Research Institute at Texas Children’s Hospital is co-first author of the study. Hyun Kyoung Lee of Baylor College of Medicine and Texas Children’s Hospital is the study’s senior and corresponding author. Ye and Lee conceived the project and designed the experiments.
A changing cellular neighborhood
To understand what was driving tumor progression, the researchers looked to neighboring cells.
A tumor is surrounded by a complex community of cells known as the tumor microenvironment. After stroke, the researchers found significant changes in that environment, including in immune cells and star-shaped glial cells called astrocytes that help maintain the normal environmental milieu of the brain and respond to injury.
The researchers identified a distinct population of tumor-associated astrocytes after stroke that showed substantially reduced calcium activity. Calcium signaling is an important element for mediating communication between cells and regulating their internal functions.
The team then tested whether changing that activity would affect the cancer. When researchers experimentally restored calcium signaling in the astrocytes, they reduced the stroke-associated increase in tumor growth and cancer cell proliferation.
The researchers also identified a protein called SLC4A4 as an important regulator of the process. Increasing the protein in astrocytes restored calcium activity, reduced tumor growth and prolonged survival in experimental models. Removing it produced the opposite effects.
Ye said the findings illustrate how glioma cells exploit changes occurring around them.
“Glioma cells can use the brain’s intrinsic repair system to progress,” said Ye, who is also a member of the department of Biomedical Sciences and Pathobiology of the Virginia-Maryland College of Veterinary Medicine. “They integrate into the brain and take advantage of those changes.”
The researchers are now investigating whether the mechanisms identified in the study could provide targets for future treatments.
“This study opens many exciting new questions,” Ye said. “We identified genes and biological pathways that may help explain how an injured brain environment influences glioma progression. Now we want to understand whether some of them could become therapeutic targets for a disease that remains largely incurable. I’m excited to bring some of these unanswered questions to my new lab at Virginia Tech’s Fralin Biomedical Research Institute and continue pursuing them there.”
Nature Cancer
Experimental study
Cells
Stroke drives glioma progression through the emergence of tumor-associated astrocytes with reduced Ca2+ activity
25-Sep-2026