The perivascular niche microenvironment in brain tumor progression

Abstract

Glioblastoma, the most frequent and aggressive malignant brain tumor, has a very poor prognosis of approximately 1-year. The associated aggressive phenotype and therapeutic resistance of glioblastoma is postulated to be due to putative brain tumor stem-like cells (BTSC). The best hope for improved therapy lies in the ability to understand the molecular biology that controls BTSC behavior. The tumor vascular microenvironment of brain tumors has emerged as important regulators of BTSC behavior. Emerging data have identified the vascular microenvironment as home to a multitude of cell types engaged in various signaling that work collectively to foster a supportive environment for BTSCs. Characterization of the signaling pathways and intercellular communication between resident cell types in the microvascular niche of brain tumors is critical to the identification of potential BTSC-specific targets for therapy.

Figure 1

The brain tumor PVN is a heterogenous composition of cell types. Some of these include astrocytes, endothelial cells, macrophages, microglia, non-tumor initiating cells and brain tumor stem-like cells (BTSCs). BTSCs are intimately connected with endothelial cells, which are a source of niche-driven signals that help maintain BTSC properties. Astrocytes are closely aligned with endothelial cells but are also found widely dispersed throughout the tumor and signal to endothelial cells as ell as other stromal cells within the tumor microenvironment to support tumor progression. Therapies targeted to the PVN and individual contributions provided by stromal cells within the tumor microenvironment. More importantly, understanding the molecular signals that mediate interactions between multiple cell types is key to successfully finding therapies targeted to the PVN.