Glioblastoma histological region-dependent differential expression of ITGA1 and NID2 genes encoding adhesion proteins to extracellular matrix

Modifications of cell adhesion and remodeling of the extracellular matrix (ECM) occur in the brain under physiological conditions (e.g., during embryonic development and in neuronal plasticity) and in pathological microenvironments (e.g., in hypoxia-dependent angiogenesis in cancer or strokes, or with the migration of the tumor cells themselves). Glioblastoma is the most common and devastating type of primary brain tumor, for which the standard of care has largely remained unaltered since 2005. Here, we wanted to study possible changes in both ITGA1 (which encodes the integrin alpha-1 protein, a receptor for collagen) and NID2 (which encodes the nidogen-2 protein in basement membranes, a protein that binds to collagen) mRNA levels based on anatomic features classified as pseudopalisading cells around necrosis (PAN), microvascular proliferation near the pseudopalisading cells (MVP), and cellular tumors (CTs) in human glioblastoma. Primary data were collected from the Ivy Glioblastoma Atlas Project, a public anatomic transcriptional database, from in situ hybridization (ISH) in glioblastoma blocks. To better compare the results, we selected images with similar architectures to PAN, MVP, and CT regions. Our results indicate that ITGA1 and NID2 genes are poorly expressed in the PAN region, which contrasts with their very high expression in the adjacent MVP zone. In addition, the ITGA1 and NID2 genes are expressed at low-medium levels in the CT areas underlying the MVP region. Other genes with the same biological function, such as BCAN and DDR1, do not show significant area-dependent transcriptional variations. Therefore, our results suggest that cell–matrix adhesion could be decreased in the PAN structure (stimulating pseudopalisading cell migration) but increased in the MVP region (promoting ECM deposition and stabilizing the vascular bed growth). Furthermore, all these results also suggest that elevated ITGA1 and NID2 expression is positively correlated with increased neovascularization, and that they could be a potential target for therapeutic intervention.