Overexpression of galectin-1 promotes cell invasion of unique migratory glioblastoma subpopulation in tumor-brain mechanical interface model

Glioblastoma (GBM) is the most common primary brain tumor characterized by extensive infiltration into peritumoral brain tissue. GBM tumors exhibit substantial intratumoral heterogeneity making it difficult to identify and target invasive cell subpopulations. In this study, an interface hydrogel model matching in vivo tissue stiffness was utilized to investigate transcriptomic changes in GBM clonal subpopulations as cells migrate across mechanical interfaces. Using single-cell RNA sequencing combined with clonal lineage tracing, unique migratory clonal subpopulations were identified that preferentially migrate at the interface. These cells exhibit a distinct pre-invasive transcriptomic profile characterized by overexpression of galectin-1, a β-galactosidase binding protein. Our findings reveal overexpression of galectin-1 is an innate characteristic of the migratory cells and that expression level is correlated to invasion rate. This study provides insight into the mechanobiological mechanisms underlying GBM invasion and potential therapeutic targets for the invasive population.