Quantitation of a “Malignancy Index” of the Relationship between Glioblastoma Microtumor Mass and Invasive Potential Using A Chicken Egg Albumen Matrix to Define Biomechanical Density Parameters that Promote Malignant Progression Malignancy Index Quantitation

Abstract

Although many factors contribute to the low translational success of pre-clinical data into human trials, one major factor is the failure of pre-clinical models to recapitulate essential physiological components of malignant tumors. An important body of clinical research indicates that the surrounding cellular microenvironment involving stromal tissue, matrix and the resident immune system play a critical role in the genesis of brain tumors of many diverse types.  The research presented in this paper specifically addresses the role of biomechanical components in the brain extracellular matrix that may play a critical role in the development and spread of central nervous system malignancies, specifically gliomas. The data suggest that unfertilized chicken egg albumen, as a novel three-dimensional culture medium, provides a biologically relevant microenvironment that can support dynamic tumor formation and growth. Chicken egg albumen supplemented culture media produced compaction effects on tumor density that varied inversely with invasion zone expansion parameters. Based on this observed relationship, a ratio was extrapolated from primary data measurements to assess more quantitatively the relationship between microtumor spheroid surface area and invasion zone diameter. The ratio of microtumor invasion zone diameter divided by microtumor surface area was calculated and designated a “Malignancy Index” based on the premise that the relationship between the peripheral invasion zone diameter relative to surface area changes reflecting changing compaction parameters of the tumor mass represents a relevant assessment of tumor invasiveness, a fundamental hallmark of malignancy.