Characterization of a glioblastoma cell line to establish a representative model of Glioblastoma Multiforme for development of immunotherapeutic targets

Abstract:

Glioblastoma Multiforme (GBM) is a fast-growing and aggressive brain tumor and accounts for 80% of primary malignant brain cancers worldwide. GBM is a devastating brain cancer that can result in death in six months or less, if untreated; hence, it is imperative to seek expert care immediately, as this can impact overall survival. There are 10,000 new annual cases of GBM diagnosed in the USA. GBM accounts for 2.5% of total cancer-related deaths and is the first cause of cancer death among those aged between 15 and 34 years. So far, conventional treatment has produced a relatively modest improvement in the overall survival of GBM patients. This can be due to the upregulation of several cytokines and chemokines that exhibit immunomodulatory effects and influence the microenvironmental landscape of GBM tumors. These factors can play a significant role in immune modulation, thus disabling anti-tumor responses and contributing to tumor progression, however, the specific roles of key cytokines and chemokines in GBM tumors have not been studied in detail. One of the cytokines secreted by GBM tumor cells is interleukin (IL)-6 that may represent a prognostic factor as well as a therapeutic target in GBM patients because high IL-6 gene expression was associated with poor survival according to the datasets derived from ‘The Cancer Genome Atlas’ and the ‘Repository of Molecular Brain Neoplasia Data’. Interlukin-6 also promotes tumor progression by acting directly on GBM cells to induce anti-apoptotic pathways and promote invasion. In this study, we have used U-87 MG cell line isolated from malignant gliomas to characterize it for the development of potential immunotherapeutic targets. We compared the basal expression of IL-6 in the U-87 MG as well as in WPMY cells, a non-malignant myofibroblast stromal cell line, and found that the basal levels of IL-6 are elevated in the U-87 MC cells compared to the basal IL-6 levels in the WPMY cells. We used IL-1α as a positive control to validate these results. The increased expression of IL-6 in the U-87 MC cells provides us a model precisely representative of GBM that will be used to identify potential molecular targets using insulin and resveratrol. The findings will further allow for immune modulation of the GBM microenvironment and thereby improved prospects for treatment of this tumor.