Mathematical Oncology

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Sebastien Motsch May 03, 2023

Self-organization in malignant brain tumors: emergence of oncostreams

Abstract

Glioblastoma multiforme (GBM) remains one of the most aggressive and untreatable cancers (median survival ~18 mo.). Tumor heterogeneity, brain invasion, and resistance to chemotherapy and radiotherapy contribute to GBM’s high mortality. We wish to examine the role of the tumor microenvironment and associated stromal structures in tumor growth, progression, and malignity. Preliminary data revealed the presence of particular histological structures within the glioma mass, which we refer to as oncostreams. Oncostreams are structures formed by elongated tumor cells measuring ~10-20 cells across and >200μm long. All types of glioma specimens examined contained oncostreams, e.g., human primary and recurrent GBM, mouse genetically induced brain tumors, human and mouse glioma stem like cells implanted orthotopically. We uncovered various functions for oncostreams. They can function as conduits for tumor growth, and as facilitators for tumor invasion into normal brain tissue. We hypothesize that oncostreams originate from the interactions between stromal cells and glioma cells. We postulate that the disruption of oncostreams will lead to inhibition of glioma growth. Our preliminary data indicate that oncostreams facilitate the intratumoral spread of other cells, such as slowly migrating human glioma stem cells. This may explain the observed correlation between the density of oncostreams with tumor malignancy. The existence and functions of oncostreams, together with results from our statistical analysis of their collective motion, strongly support the concept that oncostreams are important structures in glioma biology.