Blood Vessels in the Brain: A Signaling Hub in Brain Tumor Inflammation

Malignant brain tumors are associated with an extremely poor prognosis. Currently, only limited treatment options are available, resulting in a disappointing benefit in patient survival. In adults, primary brain tumors, mostly belonging to glioblastoma World Health Organization grade IV (GBM; the most malignant glial tumor) are characterized by infiltrative growth, necroses, and extensive vascular proliferations. GBM vessels are poorly differentiated, largely lacking regular blood–brain barrier properties. The vascular abnormalities generate a tumor microenvironment that permits sustained tumor growth by oxidative stress, metabolic changes, and augmented inflammation. Rudolf Virchow acknowledged the importance of inflammation for tumor growth as early as the middle of the 19th century. In addition to a plethora of cytokines and pro-angiogenic factors such as vascular endothelial growth factor, tumor-associated macrophages have recently been shown to secrete Wnt growth factors that were proposed to be a trigger of the so-called angiogenic switch of tumors. The Wnt/β-catenin pathway was implicated in many aspects of angiogenesis and vascular remodeling. Moreover, it has been proven to be crucial for brain angiogenesis and endothelial barrier formation during development and in brain tumors.