Glia-derived VCAM1 promotes glioma progression
Abstract
Background: The dynamic interactions between glioma cells and the tumor microenvironment (TME) drive tumor progression and therapeutic resistance. VCAM1 is known to facilitate tumor metastasis in various cancers; however, its specific function in the glioma microenvironment remains poorly defined.
Methods: To elucidate VCAM1's role in glioma, we evaluated its expression in human glioma datasets and correlated it with patient survival outcomes. Using syngeneic and primary mouse glioma models, we characterized VCAM1 expression in tumor and stromal cell populations. Furthermore, we selectively ablated VCAM1 in GLAST-positive astrocytes in a glioma-bearing mouse model to evaluate its functional impact on tumor growth and overall survival.
Results: We identified that VCAM1 is highly enriched in proliferative glioma stem cell-like cells (GSLCs); for example, 86.5% of SOX2+, 86.3% of CD133+ and 93.4% of Ki67+ cells co-expressed VCAM1 in the 73C glioma model. In the normal brain, VCAM1 is largely restricted to the vasculature, but it is notably expressed in TME-associated astrocytes. Crucially, the selective deletion of astrocytic VCAM1 significantly extended the median survival of glioma-bearing mice, such as from 52 to 66.5 days in a hippocampal GL261 model. However, this survival benefit depends on tumor location and genetic background, showing limited efficacy against aggressive hippocampal 73C tumors. Clinical data aligned with these findings, showing that lower VCAM1…
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