Intra-tumoral heterogeneity is a hallmark of glioblastoma that challenges treatment efficacy. However, the mechanisms that set up tumor heterogeneity and tumor cell migration remain poorly understood. Herein, we present a comprehensive spatiotemporal study that aligns distinctive intra-tumoral histopathological structures, oncostreams, with dynamic properties and a specific, actionable, spatial transcriptomic signature. Oncostreams are dynamic multicellular fascicles of spindle-like and aligned cells with mesenchymal properties, detected using ex vivo explants and in vivo intravital imaging. Their density correlates with tumor aggressiveness in genetically engineered mouse glioma models, and high grade human gliomas. Oncostreams facilitate the intra-tumoral distribution of tumoral and non-tumoral cells, and potentially the collective invasion of the normal brain. These fascicles are defined by a specific molecular signature that regulates their organization and function. Oncostreams structure and function depend on overexpression of COL1A1. Col1a1 is a central gene in the dynamic organization of glioma mesenchymal transformation, and a powerful regulator of glioma malignant behavior. Inhibition of Col1a1 eliminates oncostreams, reprograms the malignant histopathological phenotype, reduces expression of the mesenchymal associated genes, induces changes in the tumor microenvironment and prolongs animal survival. Oncostreams represent a pathological marker of potential value for diagnosis, prognosis, and treatment.

肿瘤内异质性是胶质母细胞瘤的一个标志，它对治疗效果提出了挑战。然而，建立肿瘤异质性和肿瘤细胞迁移的机制仍然知之甚少。在此，我们提出了一项全面的时空研究，将独特的肿瘤内组织病理学结构、肿瘤流与动态特性和特定的、可操作的空间转录组学特征对齐。Oncostreams 是具有间充质特性的纺锤状和对齐细胞的动态多细胞束，使用离体外植体和体内活体成像检测。它们的密度与基因工程小鼠神经胶质瘤模型和高级人类神经胶质瘤中的肿瘤侵袭性相关。Oncostreams 促进肿瘤和非肿瘤细胞的肿瘤内分布，并可能集体入侵正常大脑。这些分册由调节其组织和功能的特定分子特征定义。Oncostreams 结构和功能取决于 COL1A1 的过度表达。Col1a1是神经胶质瘤间充质转化动态组织的核心基因，也是神经胶质瘤恶性行为的强大调节因子。抑制Col1a1可消除肿瘤细胞，重新编程恶性组织病理学表型，减少间充质相关基因的表达，诱导肿瘤微环境的变化并延长动物存活期。Oncostreams 代表了一种对诊断、预后和治疗具有潜在价值的病理学标志物。