BACKGROUND: The complement inhibitor CSMD1 acts as a tumor suppressor in various types of solid cancers. Despite its high level of expressio
BACKGROUND: The complement inhibitor CSMD1 acts as a tumor suppressor in various types of solid cancers. Despite its high level of expression in the brain, its function in gliomas, malignant brain tumors originating from glial cells, has not been investigated. METHODS: Three cohorts of glioma patients comprising 1500 patients were analyzed in our study along with their clinical data. H4, U-118 and U-87 cell lines were used to investigate the tumor suppressor function of CSMD1 in gliomas. PDGFB-induced brain tumor model was utilized for the validation of in vitro data. RESULTS: The downregulation of CSMD1 expression correlated with reduced overall and disease-free survival, elevated tumor grade, wild-type IDH genotype, and intact 1p/19q status. Moreover, enhanced activity was noted in the neuroinflammation pathway. Importantly, ectopic expression of CSMD1 in glioma cell lines led to decreased aggressiveness in vitro. Mechanically, CSMD1 obstructed the TNF-induced NF-kB and STAT3 signaling pathways, effectively suppressing the secretion of IL-6 and IL-8. There was also reduced survival in PDGFB-induced brain tumors in mice when Csmd1 was downregulated. CONCLUSIONS: Our study has identified CSMD1 as a tumor suppressor in gliomas and elucidated its role in TNF-induced neuroinflammation, contributing to a deeper understanding of glioma pathogenesis.
Lund University, Faculty of Medicine, Department of Translational Medicine, Protein Chemistry, Malmö, Lunds universitet, Medicinska fakulteten, Institutionen för translationell medicin, Proteinkemi, Malmö, Originator, Lund University, Profile areas and other strong research environments, Other Strong Research Environments, LUCC: Lund University Cancer Centre, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Övriga starka forskningsmiljöer, LUCC: Lunds universitets cancercentrum, Originator, Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Translational Cancer Research, Brain Tumor Biology, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för translationell cancerforskning, Hjärntumörers biologi, Originator, Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Translational Cancer Research, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för translationell cancerforskning, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Malmö, Cardiovascular Research - Translational Studies, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Malmö, Kardiovaskulär forskning - translationella studier, Originator, Lund University, Profile areas and other strong research environments, Strategic research areas (SRA), EXODIAB: Excellence of Diabetes Research in Sweden, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Strategiska forskningsområden (SFO), EXODIAB: Excellence of Diabetes Research in Sweden, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Malmö, Cardiovascular Research - Immunity and Atherosclerosis, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Malmö, Kardiovaskulär forskning - immunitet och ateroskleros, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Tumor microenvironment, Tumor microenvironment, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Tumörmikromiljö, Tumörmikromiljön, Originator
