Characterization of tumor-to-tissue interactions in a mouse model of pediatric high-grade glioma.
1 IEECR
Pediatric high-grade gliomas (pHGG) are malignant brain tumors known for their aggressive behavior and tendency to spread throughout the brain, contributing significantly to cancer-related mortality in children. The molecular underpinnings of pHGG involve somatic mutations in the histone H3.3 variant, leading to distinct tumor localizations. Notably, more than 90% of pHGG, including Diffuse Intrinsic Pontine Gliomas (DIPG), carry the H3K27M mutation, posing treatment challenges due to its midline location and diffuse spreading. The mechanisms driving the rapid growth of these tumors remain a subject of debate. It's recognized that the interaction between tumor cells and their surrounding Tumor Microenvironment (TME) plays a critical role in tumor dynamics, including growth, metastasis, and therapy response. Understanding how tumor cells communicate with the TME is crucial for addressing this question.
Our study aims to explore the interactions between pHGG and the TME, shedding light on how tumors interact with their environment. We utilize a mouse model of DIPG that comprises a somatic H3.3K27M mutation, p53 loss and p53 gain-of-function mutations, delivered by in utero electroporation. Through in vivo two-photonimaging we assessed tumor cell morphology, motility and migration. This is complemented by an immunohistochemical analysis to elucidate immediate early gene expression within both tumor and non-tumor environments, revealing insights into the tumor’s influence on activity of TME cells. Our data revealed different tumor migratory characteristics and morphologies depending on the p53 gain-of-function mutations.
Understanding the characteristics of DIPGs and its interactions with the healthy brain tissue is essential for developing targeted therapies to improve overall survival. This study contributes to unraveling the complex interplay between tumor cells and their microenvironment.