Tmic-28. heterogeneous glioblastoma cell responses to tnf depend on molecular subtype

We examined how GBM molecular subtype and differentiation status influence invasive behaviors. The microglia/macrophages associated with GBM secrete a number of proinflammatory cytokines including tumor necrosis factor (TNF). In vitro, TNF up-regulates expression of the adhesion molecule VCAM-1 (Mahadev et al., PLoS One 9: e95123; 2014). We utilized a cohort of patient-derived primary glioma cell lines characterized by TCGA signature gene expression as PN or Mes (Brown et al., PLoS One 8: e7769; 2013), grown in culture with stem-like or differentiated cell properties (Brown et al., Cancer Res 69: 8886-8893; 2009), in a "dot migration assay" that recapitulates in vivobrain tumor dissemination along blood vessels and associated ECM (Baghdadchi et al., in preparation). We measured by immunofluorescence spatial dependence of tumor cell morphology and physical interactions with other tumor cells, migration, and expression of tumor adhesion molecules and other markers. VCAM-1 expression responses to TNF by proneural (PBT003) and mesenchymal (PBT017) GBM cell lines differed markedly. Specifically, VCAM-1 immunoreactivity was initially low on (PN) PBT003 cells and markedly enhanced by exposure (6 days) to TNF (10 ng/ml). In contrast, VCAM-1 immunoreactivity was initially higher on (Mes) PBT017 cells and decreased on chronic exposure to TNF. While preliminary, these observations suggest that within patient tumors, responses to activated microglia and macrophag...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: TUMOR MICROENVIRONMENT Source Type: research