High grade gliomas (HGG) are the most frequent, most aggressive, and most heterogeneous of all malignant brain tumors. HGG are heterogeneous at the histological, molecular, cellular, and supracellular level. Heterogeneity makes gliomas very hard to study and to treat. One particular tumor pathology is classified as mesenchymal differentiation, characterized by cell elongation and cell motility. We recently discovered distinctive fascicles of elongated, aligned, mesenchymal-like cells throughout mouse and human tumors, which we defined as oncostreams. Using time-lapse confocal microscopy in ex vivo slices, and in in vivo two photon imaging, we determined that cells within oncostreams are highly motile. Oncostream motility was classified based on cellular orientation into streams (cells moving back and forth), flocks (cells moving in one direction), and swarms (cells moving randomly). The molecular characteristics of oncostreams were determined by laser capture microdissection followed by RNA-sequencing, and bioinformatics. Forty three genes were differentially expressed in oncostreams; COL1A1 was overexpressed in oncostreams. Inhibition of COL1A1 in mouse gliomas, using the Sleeping Beauty transposon model, eliminated oncostreams, reduced tumor aggressiveness, inhibited proliferation, reduced tumor vasculature, and inhibited collective glioma invasion. Thus, oncostreams are morphologically and molecularly distinct, and contribute to the mesenchymal phenotype and tumor malignity. Further we recently determined that glioma cell growth in vitro also displays domains of nematic orientation (oncostreams), and topological defects, two essential characteristics of 2D liquid crystals. Liquid crystals are a mesophase of matter, between crystals, and liquids. It is increasingly recognized that biological matter can behave as liquid crystals. Topological defects are singularities of local molecular orientation, i.e., regions where orientation cannot be identified. Topological defects play a critical role in the spatiotemporal organization of active liquid crystals, and have been exploited to manipulate liquid crystal behavior. We hypothesize that manipulating brain tumor liquid crystalline behavior, will be of therapeutic importance.