The Pathobiology of Collagens in Glioma

Malignant gliomas are characterized by a diffuse infiltration into the surrounding brain parenchyma. Infiltrating glioma cells exist in close proximity with components of the tumor microenvironment, including the extracellular matrix (ECM). Whereas levels of collagens in the normal adult brain are low, in glioma, collagen levels are elevated and play a vital role in driving tumor progression. This article provides a comprehensive overview of the nature of collagens found in gliomas and offers unique insight into the mechanisms by which cancer cells interact with this ECM via cellular factors such as integrins, discoidin domain receptors, and mannose receptors. Also discussed are the major remodeling pathways of brain tumor collagen, mediated primarily by matrix metalloproteinases, and the reciprocal relationship between these enzymes and the collagen receptors. Finally, a concluding perspective is offered on how the biophysical properties of the collagen ECM, in particular, mechanical stiffness and compliance, influence malignant outcome. A better understanding of the complex molecular interactions between glioma cells and the collagen ECM will provide new avenues to combat the rampant tumor progression and chemoresistance in brain cancer patients.