Abstract
Glioblastoma (GBM) is a particularly devastating tumor with a median survival of about 16 months. Recent research has revealed novel insights into the outstanding heterogeneity of this type of brain cancer. However, all GBM subtypes share the hallmark feature of aggressive invasion into the surrounding tissue. Invasive glioblastoma cells escape surgery and focal therapies and thus represent a major obstacle for curative therapy. This review aims to provide a comprehensive understanding of glioma invasion mechanisms with respect to tumor-cell-intrinsic properties as well as cues provided by the microenvironment. We discuss genetic programs that may influence the dissemination and plasticity of GBM cells as well as their different invasion patterns. We also review how tumor cells shape their microenvironment and how, vice versa, components of the extracellular matrix and factors from non-neoplastic cells influence tumor cell motility. We further discuss different research platforms for modeling invasion. Finally, we highlight the importance of accounting for the complex interplay between tumor cell invasion and treatment resistance in glioblastoma when considering new therapeutic approaches.
Highlights
Glioblastoma (GBM) is the most prevalent and malignant primary brain tumor of adults, with a mean incidence of 7 cases per 100,000 per year and a mean overall survival of about 16 months [1]
Radio-chemotherapy, supplemented with tumor treating fields (TTFields), is the standard of care [3,4] leading to a mean overall survival of 20.9 month [4]
Invasion happens along pre-existing structures such as blood vessels, white matter tracts and the subarachnoid space [9] and is likely coordinated by specialized cells that may lead collective invasion [10,11]
Summary
Glioblastoma (GBM) is the most prevalent and malignant primary brain tumor of adults, with a mean incidence of 7 cases per 100,000 per year and a mean overall survival of about 16 months [1]. GBM is a biologically heterogenous tumor that exhibits all of the classic hallmarks of cancer [2], with significant differences between patients. Radio-chemotherapy, supplemented with tumor treating fields (TTFields), is the standard of care [3,4] leading to a mean overall survival of 20.9 month [4]. One of the clinical hallmarks of GBM is extensive infiltration of the tumor surrounding parenchyma [7,8]. GBM cells can cross tissue barriers by remodeling their own cytoskeleton and the extracellular matrix (ECM) [9] and invade as individual cells [7] or collectively [12,13]
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