Description
Glioblastoma, commonly referred to as GBM, is a highly aggressive and malignant brain tumor. GBM is typically seen in adults who are middle-aged or older. Glioblastoma constitutes almost half of all malignant primary tumors in the central nervous system, and is characterized by extensive, malformed vasculature, high levels of infiltration into surrounding nervous tissue, rapid proliferation, substantial therapeutic resistance and high recurrence. Treatment of GBM includes a partial resection followed by concurrent radiotherapy and chemotherapy. The prognosis remains dismal; the average time of survival with treatment is 12-15 months after diagnosis. A distinct feature of glioblastoma is its abnormal and heterogeneous tumor microenvironment (TME). The TME includes regions of metabolic stress, hypoxia and extracellular acidosis. Acidic conditions in tumors have been demonstrated to have a significant influence on the migration of cells, immune responses, and resistance to treatment. Cells, both healthy and malignant, sense changes in pH through a variety of specialized mechanisms. One mechanism includes proton-sensing G protein-coupled receptors (GPCRs). GPCRs convert acidic signals into intracellular responses. GPR132 is a proton-sensing GPCR that engages in immune and inflammatory signaling pathways in response to extracellular acidification. In addition, GPR132 exhibits notably more restricted expression patterns when compared to more classical GPCRs. This trait has contributed to the relatively limited characterization of GPR132 in cancer. Even so, its sensitivity to acidic microenvironments suggests a potential for relevance in solid tumors such as GBM. Direct investigation of GPR132 connectivity and function in glioblastoma, however, remains minimal, presenting a gap in current understanding. This study seeks to investigate the role of GPR132 in GBM using human clinical data to provide new insight into how tumor cells respond to increased extracellular acidity as well as contribute to invasive tumor behavior. The findings of this study may have potential implications for future therapeutic approaches.