Abstract
Ischemic stroke and brain tumors are deadly neurological disorders, with epidemiological studies revealing an increased risk of developing brain tumors in patients with a prior history of stroke. Comparative transcriptomic analysis in human data highlights a distinct enrichment of stroke-associated gene signatures in high-grade glioma, further suggesting a potential relationship between these conditions. Nevertheless, how stroke influences glioma progression remains unknown. Here we show that stroke promotes tumor progression and infiltration towards the site of injury in human and mouse glioma models, resulting in increased proliferation and reduced survival. Transcriptomic analyses identified a unique subtype of stroke-induced, tumor-associated astrocytes (TAAs) in the tumor microenvironment that display reduced Ca(2+) activity at the tumors’ leading, infiltrative edge. We found that chemogenetic stimulation of Ca(2+) activity in TAAs ameliorates stroke-induced glioma progression and identified sodium-bicarbonate cotransporter Slc4a4 as a critical factor that modulates TAA Ca(2+) activity. Collectively, our study demonstrates that stroke injury promotes glioma progression by remodeling astrocytes in the brain microenvironment, while revealing specific roles for subsets of astrocytes and their associated Ca(2+) activities in governing glioma progression.