Galectin-1 identifies a unique subpopulation of highly invasive glioblastoma cells and enables their migration

Glioblastoma (GBM), the most common primary brain tumor, is characterized by extensive infiltration into surrounding brain tissue. GBM tumors exhibit substantial intratumoral heterogeneity making it difficult to identify and target invasive cell subpopulations. Here, we use an in vitro model of the mechanical transitions at the tumor-brain interface to isolate highly invasive GBM cells from populations derived from unique patient tumors for downstream transcriptomic analysis or further culture. Using single-cell RNA sequencing combined with cell barcodes we were able to trace distinct cell lineages during migration and identify an intrinsically invasive subpopulation. This invasive subpopulation exhibits a distinct pre-invasive transcriptomic profile characterized by overexpression of galectin-1, a β-galactoside binding protein. Our findings reveal galectin-1 overexpression is an innate characteristic of invasive GBM subpopulations, where expression level positively correlates with invasion rate and inhibition of galectin-1 binding to cell surface glycoproteins effectively prevented migration. While some studies have reported that galetcin-1 aids in cell migration, this study identifies and confirms that galectin-1 expression is a pre-existing characteristic of invading GBM cells and a target to prevent tumor recurrence.