The impact of initial tumor microenvironment on imaging phenotype

Area of Science:

• Neuro-oncology
• Cancer Modeling
• Biomedical Imaging

Background:

• Accurate models of human cancer are essential for research.
• Rat xenograft brain tumors are used to model human embedded cerebral tumors.
• Contrast enhancement, a key human tumor imaging signature, is often absent in rodent models.

Purpose of the Study:

• To investigate the role of the tumor microenvironment in contrast enhancement of xenograft brain tumors.
• To identify molecular determinants of contrast enhancement in patient-derived orthotopic xenograft (PDOX) models.
• To improve the fidelity of animal models for human glioma.

Main Methods:

• Utilized patient-derived orthotopic xenograft (PDOX) models with cancer stem-like cell (CSC)-enriched neurospheres.
• Implanted cells into immune-compromised rats with and without a collagen/fibrin scaffolding matrix (Matrigel).
• Performed dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and histopathology.
• Conducted targeted proteomics to compare contrast-enhancing and non-enhancing tumors.

Main Results:

• Tumor microenvironment, specifically the presence of Matrigel, conditionally determined contrast enhancement.
• Phosphorylation of Fox038 showed differential expression between enhancing and non-enhancing tumors.
• Most proteins and post-translational modifications were comparable, highlighting specific molecular differences.

Conclusions:

• The tumor microenvironment plays a critical role in achieving contrast enhancement in rat xenograft brain tumor models.
• Differential phosphorylation of Fox038 is a key factor associated with contrast enhancement.
• These findings pave the way for developing improved animal models of human glioma.