Abstract | March 24, 2024
The Role of Tumor-Derived ANGPTL4 on Glioma Tumor Cells and Stromal Cells
Learning Objectives
- Utilize knowledge gained on ANGPTL4 modulation to enhance their approach in studying and addressing complexities related to glioma cells and stromal gene expression, contributing to a more versatile skill set in their field
Background/Knowledge Gap: Glioblastoma multiforme (GBM) exhibits the highest incidence rate among malignant brain and central nervous system tumors, displaying genotypic heterogeneity and presenting a five-year post-diagnosis survival rate of approximately 5% [1]. Despite advancements in surgical and radiotherapeutic interventions, the persistently low overall survival is primarily attributed to frequent recurrence [2]. Notably, a crucial subgroup within GBM, known as brain tumor-initiating cells (BTICs), significantly influences treatment outcomes [3-4]. ANGPTL4, a secreted glycoprotein, demonstrates high expression in GBM BTICs [5]. Activated under hypoxic conditions, ANGPTL4 is hypothesized to govern key characteristics of GBM, including cell proliferation, migration, invasion, and tumorigenic potential [6-8]. This study aims to elucidate the nuanced role of tumor-derived ANGPTL4 in both tumor and stromal cells using in vivo and in vitro models.
Methods/Design: The established glioma cell line U87 was employed, and the impact of modulating ANGPTL4 expression levels on cell doubling time and migration/invasion dynamics was investigated using a lentivirus transfection vector and short hairpin RNA. An orthotopic xenograft model was utilized to explore ANGPTL4’s effects on marker gene expression in diverse stromal cells, including endothelial cells, monocytes, and microglia.
Results/Findings: In vitro, ANGPTL4 knockdown heightened tumor cell migration and invasion activities. In the orthotopic xenograft model, ANGPTL4 knockdown led to a significant upregulation in markers associated with tumor-associated monocytes, notably Trem2 and Flor2.
Conclusions/Implications: This study advances our understanding of ANGPTL4’s role in GBM, shedding light on its impact on tumor cell behavior and stromal cell marker expression. The findings underscore the potential therapeutic relevance of targeting ANGPTL4 to refine GBM treatment modalities in clinical settings.
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