Brenda Gonzalez
Pronouns: She/Her
Research Mentor(s): Alison Affinati
Research Mentor School/College/Department: Internal Medicine / Medicine
Program: UROPF
Session: Session 1 (9:00am – 9:50am)
Authors: Brenda Gonzalez, Alison Affinati
Abstract
Glioblastoma (GBM) is one of the most fatal cancers, with a median 5-year survival rate of 6.8% and average survival rate of only 8 months after diagnosis. Prior research in the Castro-Lowenstein Lab has shown the presence of multicellular, organized groups of elongated and aligned cells, called “oncostreams,†in GBM tumors. Oncostream presence is positively correlated with tumor malignancy in both mouse models and human patients and is regulated by collagen expression. This project aims to further understand oncostream development and function by tracking and analyzing the migration patterns of oncostreams in a novel in vitro platform. After prompting in vitro oncostream formation by culturing glioma cells on laminin and poly-D-lysine coated surfaces, we conducted confocal time-lapse microscopy to capture cellular dynamics over 2-3 days. Post-imaging, we used ImageJ’s Trackmate software to track cellular trajectories. By comparing our control glioma cells (termed “NPA†with genetic mutations of NRAS, shp53, shATRX) and collagen knock-down glioma cells (termed “NPAColi†with mutations of NRAS, shp53, shATRX, shCol1a1), we found that migration persistence is significantly higher in cells containing collagen compared to without. Additionally, oncostream cells exhibit higher persistence compared to those outside oncostreams. Migration persistence is a measurement of how directed/linear the path of the cell is from Point A to Point B. Lastly, we use immunohistochemistry to probe for upregulated proteins within oncostreams compared to outside to further determine the function of oncostreams. Further understanding of the complex oncostream structures inside GBM tumors will help determine future therapeutic targets for this highly aggressive disease.
