Authors: Ananya Bharadwaj, Talia Sanazzaro, Stephanie K. Seidlits
Published: 2025-04-21
DOI: 10.1158/1538-7445.am2025-1454
Source: Full article
Glioblastoma (GBM) is an aggressive brain tumor originating from glial cells and presents difficulty in treatment. GBM are highly heterogeneous, presenting a challenge in treatment. In addition, cells migrate away often as single cells from primary tumor sites making GBM impossible to be fully resected. GBM cells adapt their behavior based on the mechanical properties of their surrounding microenvironment, making it significant to investigate gene markers associated with these mechanical changes. Our recent efforts to investigate particular gene markers included using an interface hydrogel platform that replicates the local microenvironment from the tumor edge to peritumoral tissue. Using this model we successfully separated migratory and non-migratory cells. Results from single-cell RNA (scRNA) sequencing identified gene targets that were overexpressed within the migratory group. We found the gene PTPRN2, which plays a role in vesicle trafficking and exocytosis, was overexpressed in migratory cells. This could be a promising target for future therapeutic methods to limit glioblastoma cell migration. In addition to PTPRN2, we are exploring the role of MT1X, a gene in the metallothionein family, to validate these findings. We are currently investigating the expression of the PTPRN2 and MT1X genes using GBM xenograft mouse models. We have observed PTPRN2 expression in the GBM mouse models, with the highest expression detected in migratory cells compared to non-migratory cells in soft gel conditions. In the future, we plan to perform western blot analysis to further confirm PTPRN2 and MT1X protein expression and validate their roles as potential target proteins for GBM treatment.