Glioma-induced remodeling of the neurovascular unit.
The normal BBB (blood-brain barrier) consists of a series of structures collectively known as neurovascular units, or NVU, that are composed of endothelial cells and astrocyte endfeet separated by a basal lamina at their interface. The integrity of the BBB and specifically endothelial tight junctions is maintained by interactions between these different components and the local microenvironment of the NVU. Central nervous system cancers such as gliomas disrupt the integrity of the BBB and this compromise is associated with increased tumor growth and invasion of the surrounding brain parenchyma. Because the relationship between glioma-induced BBB breakdown and glioma invasion remains poorly understood, and the host microenvironment can influence tumor cell migration, we used immunohistochemical techniques to characterize tumor associated BBB remodeling. Using an orthotopic xenograft model of glioma, we demonstrate that tumor cells induce specific changes in the composition of the basal lamina and in astrocytic components of the NVU. We suggest that these changes may be essential to understand the capacity of gliomas to regulate BBB integrity and as such, glioma invasion into brain parenchyma.
Lee
Jisook
J
Department of Surgery, Division of Trauma, 212 Dickinson Street, San Diego, CA 92103, USA.
Lund-Smith
Caren
C
Borboa
Alexandra
A
Gonzalez
Ana M
AM
Baird
Andrew
A
Eliceiri
Brian P
BP
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000473:pathology; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000473:pathology