The Microenvironmental Landscape of Brain Tumors

Abstract

The brain tumor microenvironment (TME) is emerging as a critical regulator of cancer progression in primary and metastatic brain malignancies. The unique properties of this organ require a specific framework for designing TME-targeted interventions. Here we discuss a number of these distinct features, including brain-resident cell types, the blood-brain barrier, and various aspects of the immune-suppressive environment. We also highlight recent advances in therapeutically targeting the brain TME in cancer. By developing a comprehensive understanding of the complex and interconnected microenvironmental landscape of brain malignancies we will greatly expand the range of therapeutic strategies available to target these deadly diseases.

Novel approach to temozolomide resistance in malignant glioma: connexin43-directed therapeutics

“…The major cell types that constitute the glioma microenvironment include reactive astrocytes, activated microglia, neurons, and endothelial cells, where a glial scar consisting of reactive astrocytes is usually observed to encase gliomas [25] (Figure 1). Recent studies highlight the complexities of the tumor microenvironment in mediating the etiology, progression and invasion of GBM tumors, where three major niches (hypoxic core, invasive niche at the tumor border, and perivascular niche containing blood vessels) witness distinct subsets of cellular interactions [26,27].…”

“…Recent studies highlight the complexities of the tumor microenvironment in mediating the etiology, progression and invasion of GBM tumors, where three major niches (hypoxic core, invasive niche at the tumor border, and perivascular niche containing blood vessels) witness distinct subsets of cellular interactions [26,27]. Furthermore, due to the production of tumor cell-derived and host stromal cell-derived growth factors, cytokines and matrix proteins, the tumor microenvironment represents a dynamic niche for tissue remodeling, where glioma cells can hijack molecular programs involved in normal tissue development, including immune signaling pathways, to promote their own survival and expansion [25,28,29]. …”

Neuronal activity in the glioma microenvironment

“…Understanding microenvironmental determinants of glioma growth and progression is thus a focus of current lines of research that aim to uncover new targets and strategies for treating the disease and addressing its high burden of morbidity and mortality. Prior work has endeavored to describe interactions of glioma cells with astrocytes, immune cells, and cells of the vascular system (Charles et al, 2011; Pyonteck et al, 2013; Quail and Joyce, 2017; Silver et al, 2013). Emerging research now suggests that interactions with neurons, and the direct and indirect consequences of neuronal activity, represent critically important determinants of glioma cell behavior, as well.…”

High αv Integrin Level of Cancer Cells Is Associated with Development of Brain Metastasis in Athymic Rats

“…Cancer cells with low αv integrin will loosely bind to extracellular matrix (ECM) of brain parenchyma after intracarotid or intracerebral inoculation and few of them will further develop brain lesions (31). Stapack et al (32) found that the absence of αvβ1 and αvβ3 mediated attachment to the ECM can trigger anoikis (apoptosis due the absence of cell-matrix interaction) and apoptosis.…”