Investigating CD40 and CD40L Expression and Neuronal Synaptogenesis Following Glioblastoma Invasion in Culture
Poster #: 140
Session/Time: A
Author:
Jack Conrad Campbell, MS
Mentor:
Alberto E. Musto, MD, PhD
Research Type: Basic Science
Abstract
INTRODUCTION:
Glioblastoma (GBM), an aggressive brain tumor, is associated with seizures in up to 50% of patients, suggesting tumor-driven disruption of neuronal signaling and structure. GBM modifies its environment via immune signaling and direct neuronal effects, but the mechanisms are not fully understood. One potential interaction involves CD40 and CD40L, immune signaling molecules expressed on GBM cells. Concurrently, neuronal responsiveness to such cues may be regulated by internal pathways like PTEN, a key molecule in cell growth and polarity. This study examines (1) whether both GBM cells and neurons express CD40/CD40L, enabling potential signaling, and (2) how PTEN deletion in neuronal precursors alters neuronal structure in the presence of GBM.
METHODS:
U-87 human GBM cells (ATCC® HTB-14™ cell line) and rat cortical neurons (Gibco™ A1084001) were analyzed for CD40 and CD40L protein expression using immunocytochemistry and fluorescence microscopy. Wild-type (WT) or PTEN-deleted mouse neural stem precursor cells (NSPCs) were differentiated into neurons and co-cultured with either non-tumor glia or U-87 GBM cells. Morphological changes were assessed by ICC for TUBB3 (neurons) and DAPI (nuclei).
RESULTS:
Both U-87 GBM cells and rat cortical neurons expressed CD40 and CD40L, suggesting potential immune-like signaling at the tumor-neuron interface. WT neurons grown with glia displayed well-developed arborization, but co-culture with GBM caused reduced branching and clustering. PTEN-deleted neurons exhibited impaired neurite outgrowth with glia but paradoxically increased branching in the presence of GBM.
CONCLUSION:
Glioblastoma and neurons both express CD40/CD40L, supporting the possibility of immune-mediated communication in the tumor microenvironment. Neuronal response to GBM varies by PTEN status, indicating that intrinsic signaling pathways influence tumor-driven remodeling of synaptogenesis. These findings suggest that extrinsic (CD40/CD40L) and intrinsic (PTEN) mechanisms together shape neuronal structure, excitability, and potentially tumor-associated seizures.
Glioblastoma (GBM), an aggressive brain tumor, is associated with seizures in up to 50% of patients, suggesting tumor-driven disruption of neuronal signaling and structure. GBM modifies its environment via immune signaling and direct neuronal effects, but the mechanisms are not fully understood. One potential interaction involves CD40 and CD40L, immune signaling molecules expressed on GBM cells. Concurrently, neuronal responsiveness to such cues may be regulated by internal pathways like PTEN, a key molecule in cell growth and polarity. This study examines (1) whether both GBM cells and neurons express CD40/CD40L, enabling potential signaling, and (2) how PTEN deletion in neuronal precursors alters neuronal structure in the presence of GBM.
METHODS:
U-87 human GBM cells (ATCC® HTB-14™ cell line) and rat cortical neurons (Gibco™ A1084001) were analyzed for CD40 and CD40L protein expression using immunocytochemistry and fluorescence microscopy. Wild-type (WT) or PTEN-deleted mouse neural stem precursor cells (NSPCs) were differentiated into neurons and co-cultured with either non-tumor glia or U-87 GBM cells. Morphological changes were assessed by ICC for TUBB3 (neurons) and DAPI (nuclei).
RESULTS:
Both U-87 GBM cells and rat cortical neurons expressed CD40 and CD40L, suggesting potential immune-like signaling at the tumor-neuron interface. WT neurons grown with glia displayed well-developed arborization, but co-culture with GBM caused reduced branching and clustering. PTEN-deleted neurons exhibited impaired neurite outgrowth with glia but paradoxically increased branching in the presence of GBM.
CONCLUSION:
Glioblastoma and neurons both express CD40/CD40L, supporting the possibility of immune-mediated communication in the tumor microenvironment. Neuronal response to GBM varies by PTEN status, indicating that intrinsic signaling pathways influence tumor-driven remodeling of synaptogenesis. These findings suggest that extrinsic (CD40/CD40L) and intrinsic (PTEN) mechanisms together shape neuronal structure, excitability, and potentially tumor-associated seizures.