RESEARCH
Role of the Neurogenic Niche in Glioblastoma Malignancy
Our research focuses on how components of the neurogenic niche influence the aggressiveness of glioblastoma. Specifically, we investigate the roles of cerebrospinal fluid and subventricular zone (SVZ) cells in the progression and invasiveness of human brain tumors.
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. Despite multimodal treatment approaches combining surgery, radiation, and chemotherapy, its highly invasive nature prevents complete surgical resection, leading to extremely high recurrence rates.
Tumor recurrence is driven by a subpopulation of glioblastoma cells known as brain tumor-initiating cells (BTICs). These undifferentiated cells share self-renewal and multipotent characteristics with neural stem cells but have the additional capacity to form tumors in vivo.
Previous studies show that GBMs located near the lateral ventricles (LV) are associated with poorer outcomes, including increased recurrence at distant sites. The underlying mechanisms remain unclear but may involve proximity to cerebrospinal fluid and the SVZ neurogenic niche. Our work aims to uncover the biological interactions between these components and brain tumors, providing insights into invasion and guidance of tumor cells.
Using Human Tissue to Study Tumor Cell Invasion
To better model glioblastoma invasion, our team developed an organotypic cell migration model, which uses intraoperative human brain tissue samples to study cancer cell behavior ex vivo. This system closely replicates key features of the tumor microenvironment across different brain regions and disease stages, making it the most accurate platform for observing cancer cell migration outside a living brain.
The ability of glioblastoma cells to infiltrate normal brain parenchyma is the primary barrier to curative treatment and the main reason for tumor recurrence. With this model, we can observe invasion patterns in real time under varying oxygen levels and microenvironmental conditions, using advanced video microscopy.
This research provides a powerful tool for exploring glioblastoma biology and opens opportunities for developing more personalized and effective therapeutic strategies.