Scientific reports, 2022-01, Vol.12 (1), p.1464-13, Article 1464
2022
Details
- Autor(en) / Beteiligte
- Titel
- CD97 is associated with mitogenic pathway activation, metabolic reprogramming, and immune microenvironment changes in glioblastoma
- Ist Teil von
- Scientific reports, 2022-01, Vol.12 (1), p.1464-13, Article 1464
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2022
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Glioblastoma (GBM) is the most common primary brain tumor with a median survival under two years. Using in silico and in vitro techniques, we demonstrate heterogeneous expression of CD97, a leukocyte adhesion marker, in human GBM. Beyond its previous demonstrated role in tumor invasion, we show that CD97 is also associated with upregulation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/Erk) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways in GBM. While CD97 knockout decreased Akt activation, CD97 targeting did not alter MAPK/Erk activation, did not slow GBM cell proliferation in culture, and increased levels of glycolytic and oxidative phosphorylation metabolites. Treatment with a soluble CD97 inhibitor did not alter activation of the MAPK/Erk and PI3K/Akt pathways. Tumors with high CD97 expression were associated with immune microenvironment changes including increased naïve macrophages, regulatory T cells, and resting natural killer (NK) cells. These data suggest that, while CD97 expression is associated with conflicting effects on tumor cell proliferative and metabolic pathways that overall do not affect tumor cell proliferation, CD97 exerts pro-tumoral effects on the tumor immune microenvironment, which along with the pro-invasive effects of CD97 we previously demonstrated, provides impetus to continue exploring CD97 as a therapeutic target in GBM.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-022-05259-yTitel-ID: cdi_doaj_primary_oai_doaj_org_article_401b7d931a4840b5b87625463dbdb581
- Format
- –
- Schlagworte
- 1-Phosphatidylinositol 3-kinase, Activation, Metabolic - immunology, AKT protein, Antigens, CD - genetics, Antigens, CD - metabolism, Brain cancer, Brain Neoplasms - genetics, Brain Neoplasms - immunology, Brain Neoplasms - pathology, Brain tumors, Cell culture, Cell growth, Cell Line, Tumor, Cell proliferation, Cell Proliferation - drug effects, Extracellular signal-regulated kinase, Gene Expression Regulation, Neoplastic - immunology, Gene Knockdown Techniques, Gene Knockout Techniques, Glioblastoma, Glioblastoma - genetics, Glioblastoma - immunology, Glioblastoma - pathology, Glycolysis, Humans, Immunoregulation, Kinases, Lymphocytes T, Macrophages, MAP kinase, MAP Kinase Signaling System - drug effects, MAP Kinase Signaling System - immunology, Metabolic pathways, Metabolic rate, Metabolism, Metabolites, Metabolomics, Microenvironments, Natural killer cells, Oxidative phosphorylation, Phosphatidylinositol 3-Kinases - metabolism, Phosphorylation, Proto-Oncogene Proteins c-akt - metabolism, Receptors, G-Protein-Coupled - antagonists & inhibitors, Receptors, G-Protein-Coupled - genetics, Receptors, G-Protein-Coupled - metabolism, Therapeutic targets, Tumor Microenvironment - drug effects, Tumor Microenvironment - genetics, Tumor Microenvironment - immunology